WO2006123465A1 - Drugs, food or drink for improving pancreatic functions - Google Patents
Drugs, food or drink for improving pancreatic functions Download PDFInfo
- Publication number
- WO2006123465A1 WO2006123465A1 PCT/JP2006/303709 JP2006303709W WO2006123465A1 WO 2006123465 A1 WO2006123465 A1 WO 2006123465A1 JP 2006303709 W JP2006303709 W JP 2006303709W WO 2006123465 A1 WO2006123465 A1 WO 2006123465A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- spleen
- function
- compound
- food
- endocrine cells
- Prior art date
Links
- 235000013305 food Nutrition 0.000 title claims abstract description 58
- 239000003814 drug Substances 0.000 title claims abstract description 52
- 229940079593 drug Drugs 0.000 title abstract description 6
- 230000004203 pancreatic function Effects 0.000 title abstract 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 84
- 239000004480 active ingredient Substances 0.000 claims abstract description 24
- LMYZQUNLYGJIHI-UHFFFAOYSA-N Methostenol Natural products CC1C(O)CCC2(C)C(CCC3(C(C(C)CCCC(C)C)CCC33)C)C3=CCC21 LMYZQUNLYGJIHI-UHFFFAOYSA-N 0.000 claims abstract description 10
- LMYZQUNLYGJIHI-SPONXPENSA-N 4alpha-methyl-5alpha-cholest-7-en-3beta-ol Chemical compound C[C@@H]1[C@@H](O)CC[C@]2(C)[C@@H](CC[C@@]3([C@@H]([C@H](C)CCCC(C)C)CC[C@H]33)C)C3=CC[C@H]21 LMYZQUNLYGJIHI-SPONXPENSA-N 0.000 claims abstract description 8
- AOQRDALGACAKHI-KVCRWQBISA-N (9r,10s,13r,14r,17r)-17-[(2r,5s)-5,6-dimethylheptan-2-yl]-4,10,13-trimethyl-2,3,4,5,6,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-ol Chemical compound CC1C(O)CC[C@]2(C)[C@@H](CC[C@@]3([C@@H]([C@H](C)CC[C@H](C)C(C)C)CC[C@H]33)C)C3=CCC21 AOQRDALGACAKHI-KVCRWQBISA-N 0.000 claims abstract description 7
- AOQRDALGACAKHI-UHFFFAOYSA-N 4-methylergost-7-en-3-ol Natural products CC1C(O)CCC2(C)C(CCC3(C(C(C)CCC(C)C(C)C)CCC33)C)C3=CCC21 AOQRDALGACAKHI-UHFFFAOYSA-N 0.000 claims abstract description 7
- IYIFZADLIMVECH-QYQNSBOUSA-N (9r,10s,13r,14r,17r)-17-[(2r,5r)-5-ethyl-6-methylheptan-2-yl]-4,10,13-trimethyl-2,3,4,5,6,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-ol Chemical compound CC1C(O)CC[C@]2(C)[C@@H](CC[C@@]3([C@@H]([C@H](C)CC[C@@H](CC)C(C)C)CC[C@H]33)C)C3=CCC21 IYIFZADLIMVECH-QYQNSBOUSA-N 0.000 claims abstract description 4
- IYIFZADLIMVECH-UHFFFAOYSA-N 4-methylstigmast-7-en-3-ol Natural products CC1C(O)CCC2(C)C(CCC3(C(C(C)CCC(CC)C(C)C)CCC33)C)C3=CCC21 IYIFZADLIMVECH-UHFFFAOYSA-N 0.000 claims abstract description 4
- 210000000952 spleen Anatomy 0.000 claims description 100
- 210000003890 endocrine cell Anatomy 0.000 claims description 52
- 230000003393 splenic effect Effects 0.000 claims description 37
- 239000000203 mixture Substances 0.000 claims description 33
- 241000196324 Embryophyta Species 0.000 claims description 27
- 230000006872 improvement Effects 0.000 claims description 27
- 239000000284 extract Substances 0.000 claims description 25
- 125000004432 carbon atom Chemical group C* 0.000 claims description 19
- 238000004519 manufacturing process Methods 0.000 claims description 19
- 238000000034 method Methods 0.000 claims description 19
- 239000000126 substance Substances 0.000 claims description 16
- 235000011399 aloe vera Nutrition 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
- 241000234280 Liliaceae Species 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 239000003960 organic solvent Substances 0.000 claims description 9
- 241001116389 Aloe Species 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 6
- 235000013361 beverage Nutrition 0.000 claims description 3
- 125000004922 2-methyl-3-pentyl group Chemical group CC(C)C(CC)* 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 15
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 60
- 230000006870 function Effects 0.000 description 57
- 239000000523 sample Substances 0.000 description 41
- 238000012360 testing method Methods 0.000 description 35
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- 102000004877 Insulin Human genes 0.000 description 30
- 108090001061 Insulin Proteins 0.000 description 30
- 229940125396 insulin Drugs 0.000 description 30
- 210000004027 cell Anatomy 0.000 description 26
- 210000003372 endocrine gland Anatomy 0.000 description 23
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 18
- 201000010099 disease Diseases 0.000 description 16
- 241000699670 Mus sp. Species 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 230000009471 action Effects 0.000 description 11
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 10
- 230000036541 health Effects 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 150000003839 salts Chemical class 0.000 description 9
- 235000002961 Aloe barbadensis Nutrition 0.000 description 8
- 244000186892 Aloe vera Species 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 8
- 230000007423 decrease Effects 0.000 description 8
- 206010012601 diabetes mellitus Diseases 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 238000011282 treatment Methods 0.000 description 7
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 6
- -1 alkyl cholestanes Chemical class 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 239000008103 glucose Substances 0.000 description 6
- 238000002372 labelling Methods 0.000 description 6
- 230000001681 protective effect Effects 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 5
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 230000004064 dysfunction Effects 0.000 description 5
- 239000011259 mixed solution Substances 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 206010058339 Splenitis Diseases 0.000 description 4
- 230000003915 cell function Effects 0.000 description 4
- 239000013068 control sample Substances 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 208000019229 Spleen disease Diseases 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 210000003918 fraction a Anatomy 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 210000003127 knee Anatomy 0.000 description 3
- 201000001119 neuropathy Diseases 0.000 description 3
- 230000007823 neuropathy Effects 0.000 description 3
- 238000004806 packaging method and process Methods 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 208000033808 peripheral neuropathy Diseases 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 230000005982 spleen dysfunction Effects 0.000 description 3
- 208000027140 splenic disease Diseases 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- OVMVMMNHNMZUAS-UHFFFAOYSA-N 4-methyl-1,3-dithiolane-2-thione Chemical group CC1CSC(=S)S1 OVMVMMNHNMZUAS-UHFFFAOYSA-N 0.000 description 2
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 2
- 240000007474 Aloe arborescens Species 0.000 description 2
- 235000004509 Aloe arborescens Nutrition 0.000 description 2
- YDQWDHRMZQUTBA-UHFFFAOYSA-N Aloe emodin Chemical compound C1=CC=C2C(=O)C3=CC(CO)=CC(O)=C3C(=O)C2=C1O YDQWDHRMZQUTBA-UHFFFAOYSA-N 0.000 description 2
- 244000101643 Aloe ferox Species 0.000 description 2
- 235000015858 Aloe ferox Nutrition 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 2
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 2
- 208000002177 Cataract Diseases 0.000 description 2
- 206010022489 Insulin Resistance Diseases 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 102000018886 Pancreatic Polypeptide Human genes 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 208000017442 Retinal disease Diseases 0.000 description 2
- 206010038923 Retinopathy Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 208000000277 Splenic Neoplasms Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 101000983124 Sus scrofa Pancreatic prohormone precursor Proteins 0.000 description 2
- AFHJQYHRLPMKHU-CGISPIQUSA-N aloin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1C2=CC(CO)=CC(O)=C2C(=O)C2=C(O)C=CC=C21 AFHJQYHRLPMKHU-CGISPIQUSA-N 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 239000012156 elution solvent Substances 0.000 description 2
- 210000003499 exocrine gland Anatomy 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 210000002196 fr. b Anatomy 0.000 description 2
- 210000000540 fraction c Anatomy 0.000 description 2
- 230000008717 functional decline Effects 0.000 description 2
- 235000013376 functional food Nutrition 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 150000002314 glycerols Chemical class 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 201000001421 hyperglycemia Diseases 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 230000003914 insulin secretion Effects 0.000 description 2
- 208000017169 kidney disease Diseases 0.000 description 2
- 230000002475 laxative effect Effects 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 235000016709 nutrition Nutrition 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000008816 organ damage Effects 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 238000009160 phytotherapy Methods 0.000 description 2
- 239000000419 plant extract Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000003449 preventive effect Effects 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 201000002471 spleen cancer Diseases 0.000 description 2
- 210000004989 spleen cell Anatomy 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- ZLCOWUKVVFVVKA-WDSKDSINSA-N (2r)-3-[[(2r)-2-acetamido-2-carboxyethyl]disulfanyl]-2-aminopropanoic acid Chemical compound CC(=O)N[C@H](C(O)=O)CSSC[C@H](N)C(O)=O ZLCOWUKVVFVVKA-WDSKDSINSA-N 0.000 description 1
- FRWNAQDBODEVAL-VMPITWQZSA-N (5e)-5-[(4-nitrophenyl)methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one Chemical compound C1=CC([N+](=O)[O-])=CC=C1\C=C\1C(=O)NC(=S)S/1 FRWNAQDBODEVAL-VMPITWQZSA-N 0.000 description 1
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 1
- ATIPVUGMJZAJPC-IMUDCKKOSA-N (8s,9s,10r,13r,14s,17r)-17-[(2r,5r)-5,6-dimethylheptan-2-yl]-10,13-dimethyl-1,2,4,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one Chemical compound C1C=C2CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CC[C@@H](C)C(C)C)[C@@]1(C)CC2 ATIPVUGMJZAJPC-IMUDCKKOSA-N 0.000 description 1
- HPJKMKFYRFNYKI-KMBWXDHGSA-N (9R,10S,13R,14R,17R)-17-[(2R,5R)-5-ethyl-6-methylheptan-2-yl]-4,10,13-trimethyl-2,3,4,5,6,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene Chemical compound CC1C2CC=C3[C@@H]4CC[C@H]([C@@H](CC[C@@H](CC)C(C)C)C)[C@]4(CC[C@@H]3[C@]2(CCC1)C)C HPJKMKFYRFNYKI-KMBWXDHGSA-N 0.000 description 1
- PUGBZUWUTZUUCP-ICUQLCECSA-N (9r,10s,13r,14r,17r)-17-[(2r,5s)-5,6-dimethylheptan-2-yl]-10,13-dimethyl-2,3,4,5,6,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-ol Chemical compound C1C(O)CC[C@]2(C)[C@@H](CC[C@@]3([C@@H]([C@H](C)CC[C@H](C)C(C)C)CC[C@H]33)C)C3=CCC21 PUGBZUWUTZUUCP-ICUQLCECSA-N 0.000 description 1
- VFYFMNCKPJDAPV-UHFFFAOYSA-N 2,2'-(5-oxo-1,3-dioxolan-4,4-diyl)diessigs Chemical compound C1N(C2)CN3CN1CN2C3.OC(=O)CC1(CC(O)=O)OCOC1=O VFYFMNCKPJDAPV-UHFFFAOYSA-N 0.000 description 1
- QNMKGMUGYVWVFQ-UHFFFAOYSA-N 2alpha-Hydroxyursolic acid Natural products CC12CC(O)C(O)C(C)(C)C1CCC1(C)C2CC=C2C3C(C)C(C)(C)CCC3(C(O)=O)CCC21C QNMKGMUGYVWVFQ-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 241000234282 Allium Species 0.000 description 1
- 241001073152 Aloe africana Species 0.000 description 1
- 241000782139 Aloe spicata Species 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 102000006303 Chaperonin 60 Human genes 0.000 description 1
- 108010058432 Chaperonin 60 Proteins 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 239000004158 L-cystine Substances 0.000 description 1
- 235000019393 L-cystine Nutrition 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 229940086609 Lipase inhibitor Drugs 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 1
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 1
- 108010025020 Nerve Growth Factor Proteins 0.000 description 1
- 102000007072 Nerve Growth Factors Human genes 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 1
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 1
- 208000026062 Tissue disease Diseases 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 229940008102 alloin Drugs 0.000 description 1
- 229940069521 aloe extract Drugs 0.000 description 1
- 235000014104 aloe vera supplement Nutrition 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000000702 anti-platelet effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- JPNZKPRONVOMLL-UHFFFAOYSA-N azane;octadecanoic acid Chemical class [NH4+].CCCCCCCCCCCCCCCCCC([O-])=O JPNZKPRONVOMLL-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 230000006696 biosynthetic metabolic pathway Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000002034 butanolic fraction Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 239000000287 crude extract Substances 0.000 description 1
- 229960003067 cystine Drugs 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 102000038379 digestive enzymes Human genes 0.000 description 1
- 108091007734 digestive enzymes Proteins 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 230000002888 effect on disease Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- HJUFTIJOISQSKQ-UHFFFAOYSA-N fenoxycarb Chemical compound C1=CC(OCCNC(=O)OCC)=CC=C1OC1=CC=CC=C1 HJUFTIJOISQSKQ-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 235000013402 health food Nutrition 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 229940126904 hypoglycaemic agent Drugs 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 150000003893 lactate salts Chemical class 0.000 description 1
- ZQIOPEXWVBIZAV-ZKYCIREVSA-N lanostane Chemical group CC([C@@H]1CC2)(C)CCC[C@]1(C)[C@@H]1[C@@H]2[C@]2(C)CC[C@H]([C@H](C)CCCC(C)C)[C@@]2(C)CC1 ZQIOPEXWVBIZAV-ZKYCIREVSA-N 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 239000003900 neurotrophic factor Substances 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000002669 organ and tissue protective effect Effects 0.000 description 1
- 239000000082 organ preservation Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000008050 pain signaling Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000865 phosphorylative effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 210000004044 posterior horn cell Anatomy 0.000 description 1
- 229940090181 propyl acetate Drugs 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 239000013014 purified material Substances 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 150000003873 salicylate salts Chemical class 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 210000002955 secretory cell Anatomy 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229950005143 sitosterol Drugs 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 210000002325 somatostatin-secreting cell Anatomy 0.000 description 1
- 210000004988 splenocyte Anatomy 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 229940031439 squalene Drugs 0.000 description 1
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 150000003648 triterpenes Chemical class 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000002137 ultrasound extraction Methods 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 208000037911 visceral disease Diseases 0.000 description 1
- 230000007371 visceral function Effects 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 238000003809 water extraction Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Preparation or treatment thereof
- A23L2/52—Adding ingredients
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
- A23L33/11—Plant sterols or derivatives thereof, e.g. phytosterols
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/886—Aloeaceae (Aloe family), e.g. aloe vera
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
Definitions
- the present invention relates to a medicament or food and drink for improving spleen function, which comprises a compound that can be safely ingested and that has a protective effect on splenic endocrine gland cells or an improved function of splenic endocrine gland cells.
- the spleen is an organ composed of endocrine glands called splenocytes (Island of Langerhans) and exocrine glands that secrete digestive enzymes.
- splenocytes Island of Langerhans
- ⁇ -cells ⁇ -cells
- ⁇ -cells pancreatic polypeptide cells, etc.
- pancreatic polypeptide cells etc. on the islets of Langeron, which have a great influence on the control of blood glucose and metabolism.
- ⁇ cells play a particularly important role as cells that produce insulin.
- Splenic dysfunction is an endocrine gland of the spleen! / ⁇ refers to a condition in which exocrine gland function is reduced or abnormally increased.
- Prior art therapeutic agents for spleen dysfunction include BDNF and other neurotrophic factors as active ingredients (Patent Document 1), glycerin derivative as an active ingredient (Patent Document 2), spleen function improving agent containing Buttercell Phosphate Protein or its mutein (Patent Document 3).
- BDNF is released from the central end of small DRG-euron together with other transmitters during inflammation and neuropathy, and is involved in promoting pain signaling by tyrosine phosphorylating NMDA receptors on dorsal horn cells. (Non-patent document 2), and there is a limit to actual use.
- the glycerin derivative disclosed in Patent Document 2 is a compound described in Patent Document 4, and has DIC, shock, allergy, acute knee inflammation having antiplatelet activity factor (PAF) action, Prevention of cerebral spasm during subarachnoid hemorrhage 'therapeutic agent', preventing / treating / improving organ damage caused by organ preservation under ischemic conditions, blood reperfusion after transplantation or blood flow disturbance due to surgery, etc. Although it has been found to have preventive, therapeutic and ameliorating effects on organ damage, it is difficult to say that this drug is suitable for chronic spleen diseases without these symptoms. .
- PAF antiplatelet activity factor
- a spleen function improving agent comprising a beta-monocell phosphate protein or a mutein thereof disclosed in Patent Document 3 acts on undifferentiated spleen stem cells to produce spleen ⁇ cells that produce insulin.
- the effect is not expected in the dry state.
- the mRNA of this protein has been detected in various organs other than the brain, such as the liver, kidneys, and spleen. However, since the details of its function are hardly clarified, it can be used immediately in the clinic. It's hard to say.
- a technique using a triterpene glycoside as an active ingredient for example, a prophylactic agent for diabetes containing a glycoside extracted from gymnemy drum as an active ingredient (Patent Document 5), corosolic acid extracted from vanapa And a composition for improving metabolism (Patent Document 6), a lipase inhibitor (Patent Document 7), and a triterpene derivative having immunosuppressive activity (Patent Document 8).
- Patent Document 9 a compound having a lanostane skeleton or a 3,4-secolanostan skeleton has an insulin action enhancing activity. It enhances the action of insulin in the regulation of spleen, and its effect on diseases in the spleen is unknown.
- alkylcholestene does not contain a double bond in the steroid basic skeleton.
- Patent Document 10 3-one and 24 alkyl cholestanes 3-on force group force selected compounds, or 5-campesten-3-one having a double bond at the 5-6 position, which is different from the compound of the present invention, has been disclosed as a hypoglycemic agent (Patent Document 10).
- oral phenol (a kind of stereoisomer of 4-methylcholest-7en-3ol) is known to be an intermediate in the biosynthetic pathway starting from squalene in plants (non-patent literature). 3).
- the prior art of this compound is only related to the biosynthesis system of rofenol (Non-patent Document 4), and its use is completely unknown.
- the genus Aloe is a plant group that includes aloe vera (Aloe barbadensis Miller) and yellow aloe (Aloe arbor escen Miller var. Natalensis Berger).
- Prior art documents relating to the use of genus plants include immunomodulating polysaccharides (Patent Document 11), an immunosuppressant improving agent characterized by containing an aloe extract butanol fraction or alloin (Patent Document 12), HSP60 Alloin derivative-containing synthesis inhibitors of proteins belonging to the family (Patent Documents 13 to 15), lectin-active protein derived from aloe leaf skin (Patent Document 16), and those related to blood glucose level improvement (Non-Patent Documents 5 to 7, Patent Document) 17-20) etc. are disclosed.
- Patent Document 1 International Publication Number WO00Z62796
- Patent Document 2 JP 07-285866 A
- Patent Document 3 Japanese Patent Application Laid-Open No. 09-188630
- Patent Document 4 Japanese Patent Laid-Open No. 10-045604
- Patent Document 5 Japanese Patent Laid-Open No. 05-247086
- Patent Document 7 JP 09-040689 A
- Patent Document 8 Special Table of Japanese Patent Publication 11--511482
- Patent Document 9 JP 10-330266 A
- Patent Document 10 JP 2003-048837 A
- Patent Document 11 Special Table 2001--520019
- Patent Document 12 JP 08-208495 A
- Patent Document 13 JP-A-10-120576
- Patent Document 14 JP 10-045604 A
- Patent Document 15 JP 10-0336271 A
- Patent Document 16 JP 09-059298 A
- Patent Document 17 Japanese Patent Application Laid-Open No. 60--214741
- Patent Document 19 U.S. Pat.No. 4598069
- Patent Document 20 US Patent Application Publication No. 2003Z0207818
- Non-Patent Document 1 "Insulin Resistance”, Diabetes Current Library, published, Bunkodo, 200 Published April 17, 2004
- Non-Patent Document 2 Brain Research Rev. 40, 240-249, 2002
- Non-Patent Document 3 Biochemical Experimental Method 24 Fat Lipid Metabolism Experimental Method 174 pages, Yasuhiro Yamada Academic Publishing Center, 1989
- Non-Patent Document 4 Chem. Pharm. Bull., 624-626, 1993
- Non-Patent Document 5 Phytomedicine, III, pp. 245-248, 1996
- Non-Patent Document 6 Phytotherapy Research, 15th, 157-161, 2001
- Non-Patent Document 7 Phytotherapy Research, 7th pp. 37-42, 1993
- An object of the present invention is to protect spleen endocrine gland cells from ingredients that can be safely ingested in the diet and do not contain ingredients that are not preferred as pharmaceuticals or foods and drinks, or are easily obtained. It is to provide a medicine or food or drink suitable for improving the function of spleen endocrine cells.
- the present invention provides a medicament for improving spleen function, comprising a compound represented by the following general formula (1) as an active ingredient.
- R1 is a linear or branched alkyl group having 6 to 16 carbon atoms, and does not include any double bond, or may include one or two.
- R2 and R3 are each independently a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or a substituted alkyl group, and R4 constitutes a ring.
- the force to form C 0 together with the carbon atom to generate, or OH, -OCOCH.
- R2 and R3 are a hydrogen atom, the other is a force methyl group, and R4 is a hydroxyl group.
- the medicament of the present invention preferably has the spleen function improvement as protection of spleen endocrine gland cells or improvement of spleen endocrine gland cell functions.
- the medicine or food / beverage product preferably has R1 represented by any one of the following formulas.
- R a and R b are either H, —OH, or _CH 3.
- R c is one H, _OH, or any one CH 3.
- the compound in the medicine or food or drink, is 4-methylcholest-7-en-3-ol, 4-methylergost-7-en-3-ol, and 4-methylstigmast 7-en 3—. It is preferred that the group power that is all-power is selected.
- the medicament contains 0.001 to 10% by mass of the compound in a dry mass.
- the food or drink preferably includes 0.0001 to 1% by mass of the compound in terms of dry mass.
- the present invention further relates to a plant organic solvent extract or hot water extract containing the compound represented by the general formula (1) or a fraction thereof, wherein the compound is added in a dry mass of 0.001 to
- a medicament for improving spleen function containing a composition containing 10% by mass as an active ingredient, or a food or drink for improving spleen function containing a composition containing 0.0001 to 1% by mass of the above-mentioned compound in dry mass as an active ingredient, respectively. provide.
- the spleen function improvement is preferably a protection of spleen endocrine gland cells or a function improvement of spleen endocrine gland cells.
- the medicament or food or drink has a particularly preferred embodiment in which the plant is preferably a plant belonging to the genus Aloe.
- the present invention provides the above-mentioned food or drink with an indication that it is used for improving spleen function.
- the above-mentioned medicine or food and drink may be collectively referred to as "the medicine or food and drink of the present invention”.
- the present invention also provides use of the compound represented by the general formula (1) or a composition comprising the same in the manufacture of a medicament for improving spleen function.
- the compound is contained in an amount of 0.001 to 10% by mass in dry mass.
- the improvement of spleen function is protection of spleen endocrine gland cells or improvement of function of spleen endocrine cells! /
- the present invention is also a method for improving spleen function, comprising administering the compound represented by the chemical formula (1) or a composition containing the compound to a subject whose spleen function is to be improved.
- the improvement of spleen function is preferably protection of spleen endocrine gland cells or improvement of function of spleen endocrine gland cells.
- the composition preferably contains 0.001 to 10% by mass of the compound in terms of dry mass.
- One form of the medicament or food or drink according to the present invention is a compound represented by the general formula (1), and has an effect of improving spleen function, particularly protecting spleen endocrine cells or improving function of spleen endocrine cells. (Hereinafter, sometimes referred to as “the compound of the present invention”) as an active ingredient. Further, in another form of the medicament or food or drink of the present invention, an active ingredient is an organic solvent extract or hot water extract of a plant containing the compound of the present invention or a composition containing these fractions. .
- R1 is a linear or branched alkyl group having 6 to 16 carbon atoms and does not contain any double bond, or one or two.
- the alkyl group having 1 to 3 carbon atoms is
- a methyl group in which a methyl group, an ethyl group and the like are preferable, is particularly preferable.
- the R1 is preferably a group represented by the following formula! /.
- R a and R b are either — H, — OH, or _ CH 3.
- R c and R d are either H, —OH. Or one CH 3.
- R2 and R3 are a hydrogen atom and the other is a force methyl group.
- R4 is preferably a hydroxyl group.
- the most preferred compounds as the above compounds are 4-methylcholest-7en-3ol (formula (2)), 4-methylergost-7en-3ol (formula (3)), and 4 methyl represented by the following formulae: Stigmasto 7-en 3-ol (formula (4)).
- 4-methylcholest-7en-3ol is represented by the formula (1), wherein one of R2 and R3 is a hydrogen atom, the other is a force methyl group, R4 is a hydroxyl group, Is a group represented by the above formula (vi) (wherein Rc is —H, Rd is —CH 2).
- Ergost 7 en 3 ol is represented by the general formula (1), wherein one of R2 and R3 is a hydrogen atom, the other is a katyl group, R4 is a hydroxyl group, and R1 is represented by the formula (vi). (Wherein Rc and Rd are both —CH 2). Also 4-methylstigmast
- R2 and R3 are hydrogen atom, the other is an S methyl group, R4 is a hydroxyl group, and R1 is represented by the formula (i). It is a group.
- the medicament or food or drink of the present invention may contain any two or more of the above compounds alone or in combination! /, May!
- the compound of the present invention can be produced according to a known method for producing oral phenol (Biochemical Experimental Method 24, Fatty Fat Metabolic experiment method, Akihiro Yamada, Academic Publishing Center, p. 174, 1989).
- the compound of the present invention can be obtained, for example, by extracting from a plant containing the compound using a method such as organic solvent extraction or hot water extraction, and purifying the resulting extract.
- the compound of the present invention may be purified, or may be a composition such as a plant extract or a fraction thereof as long as it contains an effective amount of the compound.
- Examples of the plant include plants belonging to the lily family. Examples of plants belonging to the lily family include plants belonging to the genus Aloe or Allium. Aloe vera (Aloe barbadensis Miller), Aloe ferox Miller (Aloe ferox Miller), Examples include Aloe africana Miller, Aloe arborescen Miller var. Natalensis Berger, and Aloe spicata Baker. In the production of the compound of the present invention or a composition containing the same, the whole plant may be used, but mesophyll (transparent gel portion) is preferably used.
- mesophyll transparent gel portion
- Such a plant or a part thereof is preferably pulverized by using a homogenizer or the like and then liquefied and extracted with an organic solvent or hot water.
- organic solvents include alcohols such as methanol, ethanol, and butanol; esters such as methyl acetate, ethyl acetate, propyl acetate, and butyl acetate; ketones such as acetone and methyl isobutyl ketone; ethers such as jetyl ether and petroleum ether; Hydrocarbons such as xane, cyclohexane, toluene, benzene; halogenated hydrocarbons such as carbon tetrachloride, dichloromethane, and chloroform; heterocyclic compounds such as pyridine; glycols such as ethylene glycol; polyalcohols such as polyethylene glycol; -Tolyl solvent, and a mixed solution of these solvents.
- solvents may be anhydrous or may be in a water-containing state.
- an ethyl acetate Z-butanol mixed solution (3: 1) or a black mouth form Z methanol mixed solution (2: 1) is particularly preferable.
- an extraction method a method used for extraction of normal plant components can be used. Usually, 1 to 300 parts by mass of an organic solvent is used per 1 part by mass of a fresh or dried plant, and the mixture is heated to reflux at a temperature not higher than the boiling point of the solvent while stirring or shaking, or is subjected to ultrasonic extraction at room temperature. A method is mentioned.
- the crude extract can be obtained by separating the insoluble matter by an appropriate method such as filtration or centrifugation.
- the extract can be purified by various types of chromatography, for example, normal phase or reverse phase silica gel column chromatography.
- reverse-phase silica gel column chromatography when a hexane / Zethyl acetate mixture (4: 1) is used as an elution solvent, the compound of the present invention is eluted as the first fraction.
- the obtained fraction can be further purified by HPLC or the like.
- the compound used in the present invention can be obtained by a chemical synthesis method, a microorganism, an enzyme, or the like. It may be produced by a biological method or an enzymatic method used.
- the compound of the present invention has an effect of improving spleen function, in particular, protecting spleen endocrine cells or improving function of spleen endocrine cells. It can be used as an active ingredient of a medicine or food and drink for improving spleen function, particularly protecting spleen endocrine gland cells or improving function of spleen endocrine cells.
- protection of splenic endocrine cells means protecting splenic endocrine cells from degeneration caused by various causes, or preventing a decrease in the ability of splenic endocrine cells to produce insulin. means.
- improvement of the function of spleen endocrine gland cells means enhancement of insulin production capacity of spleen endocrine gland cells whose insulin production capacity has decreased.
- Degeneration of splenic endocrine cells, or protection of splenic endocrine cells or improvement of splenic endocrine cells can be evaluated by microscopic observation of a spleen tissue section of an animal or measurement of insulin in serum.
- the compound of the present invention can prevent a decrease in the insulin production ability of spleen endocrine gland cells, or can increase the insulin production ability of spleen endocrine gland cells having a reduced insulin production ability.
- mice used in the examples described later are known to show spleen damage as they age (Science, 153, 1127-1128, 1966). Although it has been reported that the administration of N-acetyl-L-cystine, vitamin C and vitamin E, which are antioxidant compounds, can partially prevent a decrease in the number of j8 cells in the spleen. (Diabetes, 48, 2398-2406, 1999), N-acetylyl L-cystine alone is 100gZ60kg, and a very large dose is expected. On the other hand, the present invention can be expected to exert an effect of protecting the splenic endocrine cells or improving the function of the splenic endocrine cells at a low dose.
- the medicament of the present invention is a disease caused by a decrease in the function of splenic endocrine cells, such as acute splenitis, chronic splenitis, type I diabetes, splenic dysfunction in type 1 diabetes, senile insulin secretion.
- Active ingredient of therapeutic or preventive agent for diseases such as spleen hypofunction associated with decline can be used as Further, since the compound of the present invention has low toxicity, it can be used in combination with an antitumor agent in the treatment of spleen cancer.
- the medicament of the present invention preferably excludes those used for improving hyperglycemia among diseases associated with decreased insulin production ability.
- the bark of aloe vera contains barbaroin and aloe emodin having a laxative action, and it is considered unpreferable as a medicine or food or drink that does not expect a laxative action. Accordingly, the composition containing the compound of the present invention preferably does not contain these components. Also, aloe vera mesophyll or a crushed product thereof can be used as an active ingredient of a medicine for protecting splenic endocrine cells or improving the function of splenic endocrine cells.
- the compound of the present invention can be used as it is as an active ingredient of the medicament or food or drink of the present invention.
- an organic solvent extract or hot water extract of a plant containing the compound of the present invention or a fraction thereof (hereinafter referred to as “extract etc.”) may be used as an active ingredient of a medicine or food and drink.
- extract etc. organic solvent extract or hot water extract of a plant containing the compound of the present invention or a fraction thereof
- the extract or the like may contain two or more compounds of the present invention.
- the extract or the like may be in the form of a solution, which may be stored or used as a powder after freeze-drying or spray-drying by a conventional method.
- the medicament of the present invention can be administered orally or parenterally by using the compound of the present invention or a composition such as an extract containing the same as it is or in combination with a pharmaceutically acceptable pharmaceutical carrier. It can be administered to mammals including humans.
- the compound of the present invention can be converted to a pharmaceutically acceptable salt.
- Pharmaceutically acceptable salts include both metal salts (inorganic salts) and organic salts, a list of which is listed as “Remington's Fat ⁇ Mash ⁇ Ical, Sayen ' ⁇ S Remingtons Pharmaceutical Sciences. No. 1 / Edition, page 1418, 1985 ”.
- inorganic acid salts such as hydrochloride, sulfate, phosphate, diphosphate, hydrobromide and sulfate, malate, maleate, fumarate, tartrate, succinate
- Organic acids such as acid salts, citrates, acetates, lactates, methanesulfonates, p-toluenesulfonates, pamoates, salicylates and stearates are included without limitation.
- it can be a salt of a metal such as sodium, strength rhodium, calcium, magnesium and aluminum, or a salt with an amino acid such as lysine.
- solvates such as hydrates of the above compounds or pharmaceutically acceptable salts thereof are also included in the present invention.
- the pharmaceutical preparation form of the present invention is not particularly limited and can be appropriately selected depending on the purpose of treatment. Specifically, tablets, pills, powders, solutions, suspensions, emulsions, granules, capsules Examples include suppositories, syrups, suppositories, injections, ointments, patches, eye drops, and nasal drops.
- excipients, binders, disintegrants, lubricants, stabilizers, flavoring agents, diluting agents that are commonly used as pharmaceutical carriers for the treatment or prevention of normal visceral diseases such as spleen Additives such as agents, surfactants, and solvents for injections can be used.
- the compound of the present invention or a composition containing the same may be used in combination with a drug having a therapeutic or prophylactic action for other spleen diseases.
- the amount of the compound of the present invention or the composition containing the same contained in the medicament of the present invention is not particularly limited and may be appropriately selected. 001 to 10% by weight, preferably 0.01 to 1% by weight. / 0 , particularly preferably 0.05 to 1% by mass.
- the medicament of the present invention is capable of preventing various diseases / complications caused by the reduced function of spleen endocrine cells and reducing the risk of these diseases' complications.
- Examples of various diseases and complications resulting from the reduced function of splenic endocrine cells include neuropathy, nephropathy, retinopathy, cataract, macrovascular disorder, diabetes and the like.
- the administration time of the medicament of the present invention is not particularly limited, and can be appropriately selected according to the treatment method for the target disease.
- the dosage form is preferably determined according to the dosage form, the patient's age, sex, other conditions, the degree of symptoms of the patient, etc.
- the dose of the active ingredient of the medicament of the present invention is appropriately selected depending on the usage, patient age, sex, degree of disease, other conditions, and the like.
- the amount of the compound of the present invention as an active ingredient is preferably from 0.001 to 50 mgZkgZ ⁇ , more preferably from 0.01 to LmgZkgZ ⁇ .
- the dry weight of the composition is preferably 0.1 to: LOOOmgZkgZ days, more preferably 1 to: LOOmgZkgZ days. Is good. In either case, it can be administered once or divided into several times a day.
- the compound of the present invention or an extract containing the compound may be contained in a food or drink (beverage or food).
- a food or drink beverage or food.
- the form and properties are not particularly limited as long as they can be taken orally without impairing the effect of the active ingredient, and using the raw materials usually used for food and drink, except for containing the active ingredient. It can be produced by a usual method.
- the amount of the compound of the present invention or an extract containing the compound of the present invention contained in the food or drink of the present invention is not particularly limited and may be appropriately selected.
- this 0.0001 to 1 mass 0/0, preferably ⁇ [or 0.001 to 1 mass 0/0 is given to the special [this preferably ⁇ [or 0.005 to 1 mass 0/0 Good.
- the food and drink of the present invention can be used for various purposes such as protecting splenic endocrine cells or improving the function of splenic secretory cells.
- Uses such as food and drink that are useful for removal can be exemplified.
- protection of spleen endocrine gland cells or improvement of function of spleen endocrine gland cells refers to various health damages caused by the reduced function of spleen endocrine gland cells.
- the food and drink of the present invention is a disease caused by a decrease in function of splenic endocrine cells, such as acute splenitis, chronic splenitis, type I diabetes, spleen dysfunction in type 2 diabetes, senile insulin secretion. It is useful for preventing diseases such as hyposplenic function associated with the decrease. Furthermore, the food and drink according to the present invention can prevent various diseases / complications caused by the reduced function of spleen endocrine gland cells and reduce the risk of these diseases' complications.
- the food and drink of the present invention is also useful for patients who have been administered an antitumor agent in the treatment of spleen cancer.
- Examples of various diseases and complications resulting from the decreased function of splenic endocrine cells include neuropathy, nephropathy, retinopathy, cataract, macrovascular disorder, diabetes and the like.
- the food or drink of the present invention is a food or drink with an indication that it is used for protecting splenic endocrine cells or improving the function of splenic endocrine cells, for example, "protecting splenic endocrine cells or spleen” ⁇ Food or drink containing a compound that has the effect of protecting splenic endocrine cells or improving splenic endocrine cells '' indicated to improve the function of endocrine cells, or ⁇ protecting splenic endocrine cells or improving the function of splenic endocrine cells '' Food and drink containing plant extract labeled as "For food and drink containing aloe vera extract, described as protecting splenic endocrine cells or improving function of splenic endocrine cells", etc. It is preferable.
- the "display” means all acts for informing the consumer of the use, and if the display can recall and analogize the use, the purpose of the display, Regardless of the content, the object to be displayed, the medium, etc., all correspond to the “display” of the present invention. However, it is preferable to display it in such an expression that the consumer can directly recognize the use.
- the act of describing the above-mentioned use in the product or the product packaging relating to the food or drink of the present invention the product or the product packaging describing the above-mentioned use is transferred, and displayed for delivery, transfer or delivery Display or distribute the above uses in the acts of importing, advertisements on products, price lists or transaction documents, or distributing them, or describing the above uses in the contents of these information (such as the Internet) ) Examples of activities provided by the method.
- the display is a display approved by the government or the like (for example, a display that is approved based on various systems determined by the government and is performed in a manner based on such approval).
- a display that is approved based on various systems determined by the government and is performed in a manner based on such approval In particular, it is preferable to display on materials such as packaging, containers, catalogs, pamphlets, POP, etc., and other documents.
- indications such as health foods, functional foods, enteral nutritional foods, special-purpose foods, nutritional functional foods, quasi-drugs, etc. can be exemplified, and others by the Ministry of Health, Labor and Welfare Approved indications, for example, indications approved by foods for specified health use and similar systems can be exemplified. Examples of the latter include labeling as food for specified health use, labeling as conditionally specified food for specified health use, labeling that affects the structure and function of the body, labeling for reducing disease risk, etc.
- Speaking of health promotion law enforcement regulations (April 30, 2003 Ministry of Health, Labor and Welfare Ordinance No. 86) labeling as food for specified health use (especially labeling of health use), and similar
- the display can be listed as a typical example.
- the Z butanol mixture was recovered.
- the weight of the ethyl acetate Z butanol mixture extract obtained by concentrating the ethyl acetate Z butanol mixture under reduced pressure was 13.5 g.
- silica gel 60 manufactured by Merck & Co., Ltd.
- the column is packed and 13 g of the extract is dissolved in 1 ml of chloroform Z methanol mixture (1: 1) and adsorbed on the column.
- Increase the methanol concentration step-by-step using a mixture of Kuroguchi Form / Methanol (Kuroguchi Form: Methanol 100: 1, 25: 1, 10: 1, 5: 1 and 1: 1).
- the crudely purified material (crude product 1) containing the compound of the present invention was 3 g.
- each extract was dissolved in 1 ml of Kloform-form Z methanol mixture (1: 1), passed through a column packed with 100 g of silica gel 60 and adsorbed on the column. After that, elution was performed with 1100 ml of hexane Z acetyl acetate mixture (4: 1).
- the elution fraction was fractionated in order of 300 ml (fraction A), 300 ml (fraction B), and 500 ml (fraction C).
- the yield of each fraction after removal of the solvent was fraction A: 0.6 g, fraction B: 1.35 g, and fraction C: 0.15 g.
- the purpose of this study is to evaluate the protective effect of endocrine cell function (insulin-producing ability) of compounds with oral phenol skeleton using dbZ db mice, which are known as model animals for spleen hypofunction or spleen tissue damage. Went to.
- Test sample 1 4-methyl cholest 7-en 3 ol produced in the above production example, test sample 2, 4-methyl ergost-7-en 3 ol, test sample 2, and 4-methyl stigmasto 7-en 3-ol was designated as test sample 3.
- mice 6-week-old male dbZdb mice (purchased from Claire Japan) were used. The mice were divided into 7 groups per group. Each test sample was dissolved in DMSO and then adjusted to 0.1 or ⁇ / z gZml with physiological saline. The final DMSO concentration was adjusted to 0.2%. One ml each of the spleen disorder model mice was orally administered once a day using a sonde for 42 consecutive days. On day 43 of continuous administration, the amount of insulin in the serum was measured using a Levis Insulin Mouse ELISA kit (manufactured by Shibayagi).
- Table 1 shows the amount of insulin in serum on day 43 of continuous sample administration.
- test sample 1 test sample 2 or test sample 3 is administered at a concentration of 1 ⁇ gZ
- the serum insulin level is 184%, 210% and 211% of the negative sample, respectively, due to protection against spleen damage
- a protective effect on spleen function insulin production ability
- no significant protective effect on spleen function was observed.
- no side effects were seen from the weight and pathological findings.
- Test sample 1 (0.g) 2.33 i 1.23 ⁇ 0.19>
- Test sample 2 (g) 4.17 Sat 2.23 ⁇ 0.04 *>
- Test sample 2 (O.l g) 2.32 + 1.52 ⁇ 0.27>
- Test sample 3 (0.g) 2.23 + 0.68 ⁇ 0.17>
- Test sample 1 4-methyl cholest 7-en 3 ol produced in the above production example, test sample 2, 4-methyl ergost-7-en 3 ol, test sample 2, and 4-methyl stigmasto 7-en 3-ol was designated as test sample 3. Moreover, / 3-sitosterol (manufactured by Tama Seikagaku) was used as a control sample.
- mice 6-week-old male dbZdb mice (purchased from Claire Japan) were used. The mice were divided into 7 groups per group. Each test sample was dissolved in DMSO and then adjusted to 1 gZml with physiological saline. The final DMSO concentration was adjusted to 0.2%. Each model mouse was orally administered once a day using a sonde for 1 day, 42 ml for 42 days. On day 43 of continuous administration, the spleen was removed, divided into three parts upstream, midstream, and downstream from the duodenum side, fixed with formalin solution, and a paraffin block was prepared according to a conventional method. Section slides were prepared from paraffin blocks and stained with hematoxylin-eosin.
- Table 2 shows the number of la isles in the knee slices on the 43rd day of continuous sample administration
- Table 3 shows the maximum area of la isles.
- the number of la islets in the spleen was 188%, 159%, and 150% of the number of la islets in the negative sample-treated mice, respectively. There was a lot of power in this.
- the maximum area of La Islet was 3.6 times, 4 times, and 2.8 times that of the negative sample, respectively. It turned out to be preventing the reduction of La Island.
- mice administered with the control sample there was no difference in the number and the maximum area of La Islet, and the spleen tissue protective effect was not shown. From these results, 4-methylcholest 7-en-3-ol, 4-methylergost 7-en 3-ol, and 4-methyl stigmast 7-en 3-ol are spleen tissues, especially endocrine cells. It became clear that it has a protective effect.
- Test sample 1 (l g) 75.7 Sat 24.7 ⁇ 0.008 *>
- Test sample 3 (l g) 60.41 11.6 ⁇ 0.004 *>
- the medicament and food and drink of the present invention can be safely administered or ingested, and have an action of protecting spleen endocrine cells and improving function.
- the active ingredients of the medicament and food and drink of the present invention can also be produced as a plant that can be safely ingested and easily obtained, for example, a plant of Liliaceae such as Aloe bar badensis Miller.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Botany (AREA)
- Mycology (AREA)
- Organic Chemistry (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Steroid Compounds (AREA)
Abstract
Use of compounds having pancreatic function improving activities, for example, 4-methylcholest-7-en-3-ol, 4-methylergost-7-en -3-ol, and 4-methylstigmast-7-en-3-ol in drugs, food or drink for improving pancreatic functions as the active ingredient.
Description
明 細 書 Specification
滕臓機能改善のための医薬又は飲食品 Medicinal or food / drinks for improving visceral function
技術分野 Technical field
[0001] 本発明は、安全に摂取でき、尚且つ脾臓内分泌腺細胞の保護または脾臓内分泌 腺細胞の機能改善効果を有する化合物を含む、脾臓機能改善のための医薬又は飲 食品に関する。 背景技術 [0001] The present invention relates to a medicament or food and drink for improving spleen function, which comprises a compound that can be safely ingested and that has a protective effect on splenic endocrine gland cells or an improved function of splenic endocrine gland cells. Background art
[0002] 脾臓は、脾島 (ランゲルハンス島 (ラ氏島)）と呼ばれる内分泌腺組織と、消化酵素 の分泌を行う外分泌腺組織によって構成される器官である。ランゲルノヽンス島には β 細胞、 α細胞、 δ細胞、パンクレアティックポリペプチド細胞などが存在し、血糖や代 謝の制御に大きな影響を及ぼしている。この中でも β細胞は、インスリンを産生する 細胞として特に重要な役割を担って 、る。 [0002] The spleen is an organ composed of endocrine glands called splenocytes (Island of Langerhans) and exocrine glands that secrete digestive enzymes. There are β-cells, α-cells, δ-cells, pancreatic polypeptide cells, etc. on the islets of Langeron, which have a great influence on the control of blood glucose and metabolism. Among these, β cells play a particularly important role as cells that produce insulin.
[0003] 糖尿病は日本の成人の 10%に認められる高頻度の代謝異常である力 原因の一 つとされる脾臓の β細胞障害の疫学において、境界型高血糖の個体ではもちろん β 細胞障害があるが、耐糖能が正常な個体のなかにも明らかに β細胞機能が低下した 個体が 30%混在している。また現代の日本で平均的な社会生活を送る成人は程度 の差こそあれ、高頻度にインスリン抵抗性を生ずるといわれている力 インスリン抵抗 性を生じている場合、 |8細胞機能障害を起こさない人は血糖値が上昇せず、 |8細胞 機能障害を起こす人は血糖値が正常耐糖能から境界型高血糖へと上昇すると考え られている (非特許文献 1)。 [0003] Diabetes is a frequent metabolic disorder observed in 10% of adults in Japan In the epidemiology of β-cell damage of the spleen, which is one of the causes However, among individuals with normal glucose tolerance, there are 30% of individuals with apparently decreased β-cell function. In addition, adults who live an average social life in modern Japan, to a certain extent, do not cause cellular dysfunction if they develop insulin resistance to a certain extent. Humans do not have an increase in blood glucose level, and those who have | 8 cell dysfunction are thought to have an increase in blood glucose level from normal glucose tolerance to borderline hyperglycemia (Non-patent Document 1).
[0004] 現在のところ、脾臓機能障害に対しては原因となる病態あるいは因子を取り除くこと で、 ,能の自然回復を促す治療法が用いられているが、いったん低下した脾臓の 機能を積極的に回復させる治療方法や薬剤はいまだ用いられておらず、脾臓細胞 保護剤もしくは障害を受けた脾臓細胞の改善剤が医療現場で求められている。 [0004] At present, for splenic dysfunction, treatments that promote the natural recovery of ability are used by removing the pathology or factors that cause the spleen dysfunction. However, there are no treatment methods or drugs that can be used for recovery, and there is a need in the medical field for a spleen cell protective agent or an agent for improving damaged spleen cells.
[0005] 脾臓機能障害は、脾臓の内分泌腺ある!/ヽは外分泌腺機能が低下あるいは異常に 亢進した病態を意味する。 [0005] Splenic dysfunction is an endocrine gland of the spleen! / ヽ refers to a condition in which exocrine gland function is reduced or abnormally increased.
脾臓機能障害の治療剤の先行技術には、 BDNFなどの神経栄養因子を有効成分
とするもの（特許文献 1)、グリセリン誘導体を有効成分とするもの（特許文献 2)、ベー ターセルリン酸蛋白質またはそのムテインを含有してなる脾臓機能改善剤 (特許文献 3)などがあるが、これまで BDNFは炎症時や神経障害時に他の伝達物質とともに小 型 DRG-ユーロンの中枢端より放出され、後角細胞上で NMDA受容体をチロシンリ ン酸化することで疼痛情報伝達の促進に関与していると考えられており（非特許文献 2)、実際の使用には制限があると考えられる。 Prior art therapeutic agents for spleen dysfunction include BDNF and other neurotrophic factors as active ingredients (Patent Document 1), glycerin derivative as an active ingredient (Patent Document 2), spleen function improving agent containing Buttercell Phosphate Protein or its mutein (Patent Document 3). BDNF is released from the central end of small DRG-euron together with other transmitters during inflammation and neuropathy, and is involved in promoting pain signaling by tyrosine phosphorylating NMDA receptors on dorsal horn cells. (Non-patent document 2), and there is a limit to actual use.
また、特許文献 2に開示されているグリセリン誘導体は、特許文献 4に記載されてい る化合物であって、抗血小板活性ィ匕因子 (PAF)作用を有する DIC、ショック、アレル ギー、急性膝炎、くも膜下出血時の脳攣縮等の予防 '治療剤であり、虚血状態での 臓器保存、移植後血液再灌流あるいは手術による血流障害等の過程で生じる臓器 障害を予防 ·治療 ·改善する、臓器障害予防 ·治療 ·改善効果をも有して 、ることが見 い出されたものであるが、この薬剤はこれら症状を伴わない慢性的な脾臓疾患に適 しているとは言いがたい。 In addition, the glycerin derivative disclosed in Patent Document 2 is a compound described in Patent Document 4, and has DIC, shock, allergy, acute knee inflammation having antiplatelet activity factor (PAF) action, Prevention of cerebral spasm during subarachnoid hemorrhage 'therapeutic agent', preventing / treating / improving organ damage caused by organ preservation under ischemic conditions, blood reperfusion after transplantation or blood flow disturbance due to surgery, etc. Although it has been found to have preventive, therapeutic and ameliorating effects on organ damage, it is difficult to say that this drug is suitable for chronic spleen diseases without these symptoms. .
[0007] また、特許文献 3で開示されているベータ一セルリン酸蛋白質またはそのムテイン を含有してなる脾臓機能改善剤は、未分化脾臓幹細胞に作用して、インシュリンを産 生する脾臓 β細胞への分化を促進する作用および、未分化幹細胞を脾臓の他の細 胞、例えば、パンクレアティックポリペプチドを産生する F細胞へと分ィ匕誘導させる作 用も有するものであり、未熟な細胞が枯渴した状態では効果が期待できるものではな い。加えてこの蛋白質の mRNAは、脳以外の各種臓器、例えば肝臓、腎臓、脾臓な どで検出されているが、その機能の詳細はほとんど明らかにされていないことから、臨 床で直ちに使用できるものとは言いがたい。 [0007] Further, a spleen function improving agent comprising a beta-monocell phosphate protein or a mutein thereof disclosed in Patent Document 3 acts on undifferentiated spleen stem cells to produce spleen β cells that produce insulin. Has the effect of promoting the differentiation of cells and the action of inducing undifferentiated stem cells to differentiate into other cells of the spleen, such as F cells that produce pancreatic polypeptides. The effect is not expected in the dry state. In addition, the mRNA of this protein has been detected in various organs other than the brain, such as the liver, kidneys, and spleen. However, since the details of its function are hardly clarified, it can be used immediately in the clinic. It's hard to say.
[0008] トリテルペン配糖体を有効成分とする技術としては、例えば、ギムネマイノドラムより 抽出された配糖体を有効成分とする糖尿病の予防剤 (特許文献 5)、バナパより抽出 されたコロソリン酸を有効成分として含む代謝改善方法およびそのための組成物（特 許文献 6)、リパーゼ阻害剤 (特許文献 7)、免疫抑制活性を有するトリテルペン誘導 体 (特許文献 8)が開示されている。 [0008] As a technique using a triterpene glycoside as an active ingredient, for example, a prophylactic agent for diabetes containing a glycoside extracted from gymnemy drum as an active ingredient (Patent Document 5), corosolic acid extracted from vanapa And a composition for improving metabolism (Patent Document 6), a lipase inhibitor (Patent Document 7), and a triterpene derivative having immunosuppressive activity (Patent Document 8).
[0009] また、ラノスタン骨格、又は 3, 4—セコラノスタン骨格を有する化合物に、インスリン 作用増強活性 (特許文献 9)があることが開示されているが、その効果は、脂肪細胞
の分ィ匕調節におけるインスリンの作用を増強させるものであり、脾臓における疾患に 対する効果については不明であった。 [0009] Further, it has been disclosed that a compound having a lanostane skeleton or a 3,4-secolanostan skeleton has an insulin action enhancing activity (Patent Document 9). It enhances the action of insulin in the regulation of spleen, and its effect on diseases in the spleen is unknown.
[0010] さらに、ステロイド基本骨格の部分に 2重結合を含まない 24 アルキルコレステン [0010] Furthermore, 24 alkylcholestene does not contain a double bond in the steroid basic skeleton.
3オン及び 24 アルキルコレスタン 3オン力 なる群力 選ばれる化合物、又は 本発明の化合物とは異なる 5— 6位に二重結合を持つ 5—カンペステン— 3—オンが 血糖降下剤として開示されている (特許文献 10)。 3-one and 24 alkyl cholestanes 3-on force group force selected compounds, or 5-campesten-3-one having a double bond at the 5-6 position, which is different from the compound of the present invention, has been disclosed as a hypoglycemic agent (Patent Document 10).
[0011] ところで、口フエノール（4ーメチルコレストー7 ェンー3 オールの立体異性体の 一種）は、植物におけるスクヮランから出発する生合成経路の中間体であることが知 られている（非特許文献 3)。しかし、この化合物における先行技術については、ロフ ェノールの生合成系に関するもののみであり（非特許文献 4)、その用途については 全く未知のものであった。 [0011] Incidentally, oral phenol (a kind of stereoisomer of 4-methylcholest-7en-3ol) is known to be an intermediate in the biosynthetic pathway starting from squalene in plants (non-patent literature). 3). However, the prior art of this compound is only related to the biosynthesis system of rofenol (Non-patent Document 4), and its use is completely unknown.
[0012] ユリ科アロエ属は、アロエベラ（Aloe barbadensis Miller)やキダチアロエ（Aloe arbor escen Miller var.natalensis Berger)等を含む植物群で、様々な効能があることが経験 的に知られており、アロエ属植物の用途に関する先行技術文献には、免疫修飾性多 糖類 (特許文献 11)、アロエ抽出物のブタノール画分又はァロインを含有することを 特徴とする免疫抑制改善剤（特許文献 12)、 HSP60ファミリーに属するタンパク質の ァロイン誘導体含有合成抑制剤 (特許文献 13〜15)、アロエ葉皮由来のレクチン活 性蛋白質 (特許文献 16)、及び血糖値改善に関するもの (非特許文献 5〜7、特許文 献 17〜20)等が開示されている。 [0012] The genus Aloe is a plant group that includes aloe vera (Aloe barbadensis Miller) and yellow aloe (Aloe arbor escen Miller var. Natalensis Berger). Prior art documents relating to the use of genus plants include immunomodulating polysaccharides (Patent Document 11), an immunosuppressant improving agent characterized by containing an aloe extract butanol fraction or alloin (Patent Document 12), HSP60 Alloin derivative-containing synthesis inhibitors of proteins belonging to the family (Patent Documents 13 to 15), lectin-active protein derived from aloe leaf skin (Patent Document 16), and those related to blood glucose level improvement (Non-Patent Documents 5 to 7, Patent Document) 17-20) etc. are disclosed.
特許文献 1 国際公開番号 WO00Z62796 Patent Document 1 International Publication Number WO00Z62796
特許文献 2特開平 07 - - 285866号公報 Patent Document 2 JP 07-285866 A
特許文献 3特開平 09 - 188630号公報 Patent Document 3 Japanese Patent Application Laid-Open No. 09-188630
特許文献 4特開平 10 - 045604号公報 Patent Document 4 Japanese Patent Laid-Open No. 10-045604
特許文献 5特開平 05 - - 247086号公報 Patent Document 5 Japanese Patent Laid-Open No. 05-247086
特許文献 6特開 2002- - 205949号公報 Patent Document 6 JP 2002-205949 A
特許文献 7特開平 09 - 040689号公報 Patent Document 7 JP 09-040689 A
特許文献 8特表平 11 - - 511482号公報 Patent Document 8 Special Table of Japanese Patent Publication 11--511482
特許文献 9特開平 10 - - 330266号公報
特許文献 10特開 2003 - -048837号公報 Patent Document 9 JP 10-330266 A Patent Document 10 JP 2003-048837 A
特許文献 11 特表 2001 - - 520019号公報 Patent Document 11 Special Table 2001--520019
特許文献 12特開平 08 - - 208495号公報 Patent Document 12 JP 08-208495 A
特許文献 13特開平 10 - 120576号公報 Patent Document 13 JP-A-10-120576
特許文献 14特開平 10 - 045604号公報 Patent Document 14 JP 10-045604 A
特許文献 15特開平 10 - 036271号公報 Patent Document 15 JP 10-0336271 A
特許文献 16特開平 09 - 059298号公報 Patent Document 16 JP 09-059298 A
特許文献 17特開昭 60 - - 214741号公報 Patent Document 17 Japanese Patent Application Laid-Open No. 60--214741
特許文献 18特開 2003 - - 286185号公報 Patent Document 18 JP 2003-286185 A
特許文献 19米国特許第 4598069号明細書 Patent Document 19 U.S. Pat.No. 4598069
特許文献 20米国特許出願公開第 2003Z0207818号明細書 Patent Document 20 US Patent Application Publication No. 2003Z0207818
非特許文献 1 :「インスリン抵抗性」、糖尿病カレントライブラリー、発行、文光堂、 200 4年 4月 17日発行 Non-Patent Document 1: "Insulin Resistance", Diabetes Current Library, published, Bunkodo, 200 Published April 17, 2004
非特許文献 2 :ブレイン リサーチ レビュー（Brain Res Rev)第 40卷、第 240〜249 頁、 2002年 Non-Patent Document 2: Brain Research Rev. 40, 240-249, 2002
非特許文献 3 :生物化学実験法 24 脂肪脂質代謝実験法 174ページ、山田晃弘 著 学会出版センター、 1989年 Non-Patent Document 3: Biochemical Experimental Method 24 Fat Lipid Metabolism Experimental Method 174 pages, Yasuhiro Yamada Academic Publishing Center, 1989
非特許文献 4 :ケミ 'ファム'ブル（Chem. Pharm. Bull.)、第 624〜626ページ、 1993 年 Non-Patent Document 4: Chem. Pharm. Bull., 624-626, 1993
非特許文献 5 :フィトメディシン（Phytomedicine)、第 3卷、第 245〜248ページ、 1996 年 Non-Patent Document 5: Phytomedicine, III, pp. 245-248, 1996
非特許文献 6 :フイトセラピ一'リサーチ（Phytotherapy Research)、第 15卷、第 157〜 161ページ、 2001年 Non-Patent Document 6: Phytotherapy Research, 15th, 157-161, 2001
非特許文献 7 :フイトセラピ一'リサーチ（Phytotherapy Research)、第 7卷、第 37〜42 ページ、 1993年 Non-Patent Document 7: Phytotherapy Research, 7th pp. 37-42, 1993
発明の開示 Disclosure of the invention
本発明の課題は、食経験上安全に摂取でき、かつ、入手容易な原料から、医薬又 は飲食品として好ましくない成分を含まず、かつ、脾臓内分泌腺細胞の保護または
脾臓内分泌腺細胞の機能改善に適した医薬又は飲食品を提供することである。 An object of the present invention is to protect spleen endocrine gland cells from ingredients that can be safely ingested in the diet and do not contain ingredients that are not preferred as pharmaceuticals or foods and drinks, or are easily obtained. It is to provide a medicine or food or drink suitable for improving the function of spleen endocrine cells.
[0014] 本発明者らは、上記の課題を解決すべく鋭意研究を行った結果、植物に幅広く含 まれている、口フエノールに類似の構造を持つ化合物力 安全に摂取でき、かつ、脾 臓機能改善作用を有することを見出した。本発明は、上記の知見に基づき完成され たものである。 [0014] As a result of intensive studies to solve the above-mentioned problems, the present inventors have been able to safely ingest compound spleen having a structure similar to oral phenol widely contained in plants. It was found to have a function improving action. The present invention has been completed based on the above findings.
すなわち、本発明は、下記の一般式（1)で表される化合物を有効成分として含む、 脾臓機能改善のための医薬を提供する。 That is, the present invention provides a medicament for improving spleen function, comprising a compound represented by the following general formula (1) as an active ingredient.
[0015] [化 1] [0015] [Chemical 1]
[0016] 式中、 R1は炭素原子数 6〜16の直鎖状または分枝鎖状のアルキル基であり、 2重 結合を全く含まないか、又は、 1つもしくは 2つ含んでいてもよぐヒドロキシル基及び Z又はカルボ二ル基を含んでいてもよぐ R2、 R3は各々独立に水素原子、炭素原 子数 1〜3のアルキル基、又は置換アルキル基であり、 R4は環を構成する炭素原子 とともに C = 0を形成する力、または、 OH、 -OCOCHのいずれかである。 [0016] In the formula, R1 is a linear or branched alkyl group having 6 to 16 carbon atoms, and does not include any double bond, or may include one or two. R2 and R3 are each independently a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or a substituted alkyl group, and R4 constitutes a ring. The force to form C = 0 together with the carbon atom to generate, or OH, -OCOCH.
3 Three
[0017] 前記 R2及び R3の一方が水素原子であり、他方力メチル基であり、 R4が水酸基で あることを好まし 、態様として 、る。 [0017] It is preferable that one of R2 and R3 is a hydrogen atom, the other is a force methyl group, and R4 is a hydroxyl group.
本発明の医薬は、脾臓機能改善が、脾臓内分泌腺細胞の保護又は脾臓内分泌腺 細胞の機能改善であることを好まし 、態様として 、る。 The medicament of the present invention preferably has the spleen function improvement as protection of spleen endocrine gland cells or improvement of spleen endocrine gland cell functions.
また、前記医薬又は飲食品は、前記 R1が、下記式のいずれかで表されることを好 ましい態様としている。 In addition, the medicine or food / beverage product preferably has R1 represented by any one of the following formulas.
[0018] [化 2]
-CH2-CH2-CH (-CH2-CH3) — CH (CH3) 2 [0018] [Chemical 2] -CH 2 -CH 2 -CH (-CH2-CH3) — CH (CH 3 ) 2
— CH2 - CH2_CH=C (C H 3) 2 — CH 2 -CH 2 _CH = C (CH 3 ) 2
— CH2_CH = C (CH 3) — CH (CH3) 2 — CH 2 _CH = C (CH 3 ) — CH (CH 3 ) 2
— CH2— CH2— C (=CH - CH3) - CH (CH3) 2 — CH 2 — CH 2 — C (= CH-CH 3 )-CH (CH 3 ) 2
-CH2-CH2-CH (R a) =C (CH 3) R b -CH 2 -CH 2 -CH (R a) = C (CH 3) R b
(ただし、 R a、 R bは、 H、 -OH, 又は _ C H 3のいずれかである。 ） (However, R a and R b are either H, —OH, or _CH 3. )
-CH2-CH2-CH (R c) -CH (CH3) R d -CH 2 -CH 2 -CH (R c) -CH (CH 3 ) R d
(ただし、 R c：、 R dは、 一 H、 _OH、 又は一 CH 3のいずれかである。 ） (Wherein, R c :, R d is one H, _OH, or any one CH 3.)
[0019] また、前記医薬又は飲食品は、前記化合物が、 4ーメチルコレスト 7 ェンー 3— オール、 4ーメチルエルゴスト— 7—ェンー3—オール、及び 4ーメチルスチグマストー 7—ェン 3—オール力 なる群力 選ばれることを好まし 、態様として 、る。 [0019] In addition, in the medicine or food or drink, the compound is 4-methylcholest-7-en-3-ol, 4-methylergost-7-en-3-ol, and 4-methylstigmast 7-en 3—. It is preferred that the group power that is all-power is selected.
[0020] また、前記医薬は、前記化合物を乾燥質量で 0.001〜10質量％含むことを好まし い態様としている。 [0020] Further, it is preferable that the medicament contains 0.001 to 10% by mass of the compound in a dry mass.
また、前記飲食品は、前記化合物を乾燥質量で 0.0001〜1質量％含むことを好 ましい態様としている。 In addition, the food or drink preferably includes 0.0001 to 1% by mass of the compound in terms of dry mass.
[0021] 本発明はさらに、前記一般式（1)で表される化合物を含む植物の有機溶媒抽出物 もしくは熱水抽出物又はこれらの分画物であって、前記化合物を乾燥質量で 0.001 〜10質量％含む組成物を有効成分として含む脾臓機能改善のための医薬、又は前 記化合物を乾燥質量で 0.0001〜1質量％含む組成物を有効成分として含む脾臓 機能改善のための飲食品をそれぞれ提供する。本発明の医薬は、脾臓機能改善が 、脾臓内分泌腺細胞の保護又は脾臓内分泌腺細胞の機能改善であることを好まし い態様としている。 [0021] The present invention further relates to a plant organic solvent extract or hot water extract containing the compound represented by the general formula (1) or a fraction thereof, wherein the compound is added in a dry mass of 0.001 to A medicament for improving spleen function containing a composition containing 10% by mass as an active ingredient, or a food or drink for improving spleen function containing a composition containing 0.0001 to 1% by mass of the above-mentioned compound in dry mass as an active ingredient, respectively. provide. In the medicament of the present invention, the spleen function improvement is preferably a protection of spleen endocrine gland cells or a function improvement of spleen endocrine gland cells.
[0022] 前記医薬又は飲食品は、前記植物がユリ科植物であることが好ましぐ前記ユリ科 植物がアロエ属に分類される植物であることを特に好ましい態様としている。 [0022] The medicament or food or drink has a particularly preferred embodiment in which the plant is preferably a plant belonging to the genus Aloe.
本発明は、脾臓機能改善のために用いられる旨の表示を付した上記の飲食品を提 供する。 The present invention provides the above-mentioned food or drink with an indication that it is used for improving spleen function.
[0023] 以下、上記医薬又は飲食品を、総称して「本発明の医薬又は飲食品」ということが ある。 [0023] Hereinafter, the above-mentioned medicine or food and drink may be collectively referred to as "the medicine or food and drink of the present invention".
本発明はまた、脾臓機能改善用の医薬の製造における、前記一般式 (1)で表され る化合物又はそれを含む組成物の使用を提供する。本発明の使用は、前記化合物 を乾燥質量で 0.001〜10質量％含むことを好ましい態様としている。本発明の使用
は、脾臓機能改善が、脾臓内分泌腺細胞の保護又は脾臓内分泌腺細胞の機能改 善であることを好まし!/、態様として！/、る。 The present invention also provides use of the compound represented by the general formula (1) or a composition comprising the same in the manufacture of a medicament for improving spleen function. In the use of the present invention, it is preferable that the compound is contained in an amount of 0.001 to 10% by mass in dry mass. Use of the present invention It is preferable that the improvement of spleen function is protection of spleen endocrine gland cells or improvement of function of spleen endocrine cells! /
本発明はまた、脾臓機能を改善する方法であって、前記化学式（1)で表される化 合物又はそれを含む組成物を、脾臓の機能を改善しょうとする対象に投与することを 特徴とする方法を提供する。本発明の方法は、脾臓機能改善が、脾臓内分泌腺細 胞の保護又は脾臓内分泌腺細胞の機能改善であることを好まし 、態様として 、る。 また、本発明の方法は、前記組成物が、前記化合物を乾燥質量で 0. 001〜10質量 %含むことを好ま 、態様として 、る。 The present invention is also a method for improving spleen function, comprising administering the compound represented by the chemical formula (1) or a composition containing the compound to a subject whose spleen function is to be improved. To provide a method. In the method of the present invention, the improvement of spleen function is preferably protection of spleen endocrine gland cells or improvement of function of spleen endocrine gland cells. In the method of the present invention, the composition preferably contains 0.001 to 10% by mass of the compound in terms of dry mass.
発明を実施するための最良の形態 BEST MODE FOR CARRYING OUT THE INVENTION
[0024] 次に、本発明の好ましい実施形態について詳細に説明する。ただし、本発明は以 下の好ましい実施形態に限定されず、本発明の範囲内で自由に変更することができ るものである。 [0024] Next, a preferred embodiment of the present invention will be described in detail. However, the present invention is not limited to the following preferred embodiments, and can be freely modified within the scope of the present invention.
[0025] 本発明の医薬又は飲食品の一形態は、前記一般式（1)で表される化合物であって 、脾臓機能改善作用、特に脾臓内分泌腺細胞の保護または脾臓内分泌腺細胞の機 能改善作用を持つ化合物（以下、「本発明の化合物」 、うことがある）を有効成分と して含むものである。また、本発明の医薬又は飲食品の他の形態では、本発明の化 合物を含む植物の有機溶媒抽出物もしくは熱水抽出物又はこれらの分画物を含む 組成物を有効成分として含むものである。 [0025] One form of the medicament or food or drink according to the present invention is a compound represented by the general formula (1), and has an effect of improving spleen function, particularly protecting spleen endocrine cells or improving function of spleen endocrine cells. (Hereinafter, sometimes referred to as “the compound of the present invention”) as an active ingredient. Further, in another form of the medicament or food or drink of the present invention, an active ingredient is an organic solvent extract or hot water extract of a plant containing the compound of the present invention or a composition containing these fractions. .
[0026] 前記一般式（1)中、 R1は炭素原子数 6〜16の直鎖状または分枝鎖状のアルキル 基であり、 2重結合を全く含まないか、又は、 1つもしくは 2つ含んでいてもよぐ R2、 R 3は各々独立に水素原子、炭素原子数 1〜3のアルキル基、又は置換アルキル基で あり、 R4は環を構成する炭素原子とともに C = 0を形成する力または、— OH、 -OC OCHのいずれかであることが好ましい。尚、前記炭素原子数 1〜3のアルキル基とし [0026] In the general formula (1), R1 is a linear or branched alkyl group having 6 to 16 carbon atoms and does not contain any double bond, or one or two. R2 and R3 are each independently a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or a substituted alkyl group, and R4 is a force that forms C = 0 with the carbon atoms constituting the ring. Or, it is preferably either —OH or —OC 2 OCH. The alkyl group having 1 to 3 carbon atoms is
3 Three
ては、メチル基、ェチル基等が好ましぐメチル基が特に好ましい。 In particular, a methyl group, in which a methyl group, an ethyl group and the like are preferable, is particularly preferable.
前記 R1は、下記式で表される基の!/、ずれかであることが好まし！/、。 The R1 is preferably a group represented by the following formula! /.
[0027] [化 3]
(i) 一 CH2 - CH2 - CH (-CH2-CH3) 一 CH (CH3) 2 [0027] [Chemical 3] (i) One CH 2 -CH 2 -CH (-CH 2 -CH 3 ) One CH (CH 3 ) 2
(ii) 一 CH2_CH2 - CH = C (C H 3) 2 (ii) One CH 2 _CH 2 -CH = C (CH 3 ) 2
(iii) -CH2-CH=C (CH3) - CH (CH 3) 2 (iii) -CH 2 -CH = C (CH 3 )-CH (CH 3 ) 2
(iv) -CH2-CH2-C (=CH-CH3) 一 CH (CH3) 2 (iv) -CH 2 -CH 2 -C (= CH-CH 3 ) One CH (CH 3 ) 2
(v) -CH2-CH2-CH (R a) =C (CH3) R b (v) -CH 2 -CH 2 -CH (R a) = C (CH 3 ) R b
(ただし R a、 R bは、 — H、 — OH、 又は _ C H 3のいずれかである。 ） (However, R a and R b are either — H, — OH, or _ CH 3. )
(vi) 一 CH2— CH2— CH (R c) -CH (CH 3) R d (vi) One CH 2 — CH 2 — CH (R c) -CH (CH 3 ) R d
(ただし、 R c、 R dは、 H、 -OH. 又は一 CH 3のいずれかである。 ） (However, R c and R d are either H, —OH. Or one CH 3. )
[0028] また、前記 R2及び R3は、一方が水素原子であり、他方力メチル基であることが好ま しい。さらに、 R4は水酸基であることが好ましい。 [0028] Further, it is preferable that one of R2 and R3 is a hydrogen atom and the other is a force methyl group. Further, R4 is preferably a hydroxyl group.
[0029] 前記化合物として最も好ましい化合物は、下記式で表される 4ーメチルコレスト 7 ーェンー3 オール（式（2))、 4ーメチルエルゴスト— 7 ェンー3 オール（式（3)) 、及び 4 メチルスチグマストー 7—ェン 3—オール（式（4) )である。 [0029] The most preferred compounds as the above compounds are 4-methylcholest-7en-3ol (formula (2)), 4-methylergost-7en-3ol (formula (3)), and 4 methyl represented by the following formulae: Stigmasto 7-en 3-ol (formula (4)).
[0030] [化 4] [0030] [Chemical 4]
[0031] [化 5] [0031] [Chemical 5]
[0032] [化 6]
[0032] [Chemical 6]
[0033] すなわち、 4ーメチルコレストー7 ェンー3 オールは、前記一般式（1)において 、 R2及び R3の一方が水素原子であり、他方力メチル基であり、 R4が水酸基であって 、 R1が前記式 (vi)で表される基（但し、 Rcは— H、 Rdは— CH )である。 4—メチル [0033] That is, 4-methylcholest-7en-3ol is represented by the formula (1), wherein one of R2 and R3 is a hydrogen atom, the other is a force methyl group, R4 is a hydroxyl group, Is a group represented by the above formula (vi) (wherein Rc is —H, Rd is —CH 2). 4-methyl
3 Three
ェルゴスト 7 ェン 3 オールは、前記一般式（1)において、 R2及び R3の一方 が水素原子であり、他方カ チル基であり、 R4が水酸基であって、 R1が前記式 (vi) で表される基（但し、 Rc及び Rdはともに— CH )である。また、 4—メチルスチグマスト Ergost 7 en 3 ol is represented by the general formula (1), wherein one of R2 and R3 is a hydrogen atom, the other is a katyl group, R4 is a hydroxyl group, and R1 is represented by the formula (vi). (Wherein Rc and Rd are both —CH 2). Also 4-methylstigmast
3 Three
7 ェンー 3 オールは、前記一般式（1)において、 R2及び R3の一方が水素原 子であり、他方力 Sメチル基であり、 R4が水酸基であって、 R1が前記式 (i)で表される 基である。 In the general formula (1), one of R2 and R3 is a hydrogen atom, the other is an S methyl group, R4 is a hydroxyl group, and R1 is represented by the formula (i). It is a group.
[0034] 本発明の医薬又は飲食品は、前記化合物の一種を単独で含んでいてもよぐ任意 の 2種以上を含んで!/、てもよ!/、。 [0034] The medicament or food or drink of the present invention may contain any two or more of the above compounds alone or in combination! /, May!
[0035] 口フエノールが植物に含まれていることは公知であり、公知の口フエノールの製造方 法に準じて、本発明の化合物を製造することができる（生物化学実験法 24、脂肪脂 質代謝実験法、山田晃弘著、学会出版センター、第 174ページ、 1989年)。本発明 の化合物は、例えば、同化合物を含む植物から、有機溶媒抽出法または熱水抽出 法などの方法を用いて抽出し、得られた抽出物を精製することによって、得ることがで きる。本発明においては、本発明の化合物は、精製されたものであってもよいが、同 化合物を有効量含む限り、植物の抽出物又はその分画物等の組成物であってもよ い。 [0035] It is known that oral phenol is contained in plants, and the compound of the present invention can be produced according to a known method for producing oral phenol (Biochemical Experimental Method 24, Fatty Fat Metabolic experiment method, Akihiro Yamada, Academic Publishing Center, p. 174, 1989). The compound of the present invention can be obtained, for example, by extracting from a plant containing the compound using a method such as organic solvent extraction or hot water extraction, and purifying the resulting extract. In the present invention, the compound of the present invention may be purified, or may be a composition such as a plant extract or a fraction thereof as long as it contains an effective amount of the compound.
[0036] 前記植物としては、ユリ科に属する植物が挙げられる。ユリ科に属する植物としては 、アロエ属又はァリウム属に属する植物が挙げられる。また、アロエ属植物としては、 アロエベラ (Aloe barbadensis Miller)、アロエフエロックスミラー (Aloe ferox Miller)、ァ
ロェアフリカ一ナミラー (Aloe africana Miller)、キダチアロエ (Aloe arborescen Miller var.natalensis Berger)、アロエスピカータベイカー (Aloe spicata Baker)等がが挙げら れる。本発明の化合物の又はそれを含む組成物の製造においては、前記植物の全 体を用いてもよいが、葉肉（透明ゲル部分)を用いることが好ましい。このような植物又 はその一部を、好ましくはホモジナイザー等を用いて破砕して液状ィ匕し、有機溶媒又 は熱水で抽出する。有機溶媒としては、メタノール、エタノール、ブタノール等のアル コール；酢酸メチル、酢酸ェチル、酢酸プロピル、酢酸ブチル等のエステル；アセトン 、メチルイソブチルケトン等のケトン；ジェチルエーテル、石油エーテル等のエーテル ；へキサン、シクロへキサン、トルエン、ベンゼン等の炭化水素；四塩化炭素、ジクロロ メタン、クロホルム等のハロゲンィ匕炭化水素；ピリジン等の複素環化合物、エチレング リコール等のグリコール；ポリエチレングリコール等のポリアルコール；ァセトニトリル等 の-トリル溶媒、及びこれらの溶媒の混合液等が挙げられる。また、これらの溶媒は 無水であってもよぐ含水状態であってもよい。これらの溶媒の中では、特に、酢酸ェ チル Zブタノール混合液（3 : 1)、若しくはクロ口ホルム Zメタノール混合液（2： 1)が 好ましい。 [0036] Examples of the plant include plants belonging to the lily family. Examples of plants belonging to the lily family include plants belonging to the genus Aloe or Allium. Aloe vera (Aloe barbadensis Miller), Aloe ferox Miller (Aloe ferox Miller), Examples include Aloe africana Miller, Aloe arborescen Miller var. Natalensis Berger, and Aloe spicata Baker. In the production of the compound of the present invention or a composition containing the same, the whole plant may be used, but mesophyll (transparent gel portion) is preferably used. Such a plant or a part thereof is preferably pulverized by using a homogenizer or the like and then liquefied and extracted with an organic solvent or hot water. Examples of organic solvents include alcohols such as methanol, ethanol, and butanol; esters such as methyl acetate, ethyl acetate, propyl acetate, and butyl acetate; ketones such as acetone and methyl isobutyl ketone; ethers such as jetyl ether and petroleum ether; Hydrocarbons such as xane, cyclohexane, toluene, benzene; halogenated hydrocarbons such as carbon tetrachloride, dichloromethane, and chloroform; heterocyclic compounds such as pyridine; glycols such as ethylene glycol; polyalcohols such as polyethylene glycol; -Tolyl solvent, and a mixed solution of these solvents. These solvents may be anhydrous or may be in a water-containing state. Among these solvents, an ethyl acetate Z-butanol mixed solution (3: 1) or a black mouth form Z methanol mixed solution (2: 1) is particularly preferable.
[0037] 抽出方法としては、通常の植物成分の抽出に用いられる方法を用いることができる 。通常、新鮮な植物又は乾燥植物 1質量部に対し、有機溶媒 1〜300質量部を用い て、撹拌又は振盪しながら、溶媒の沸点以下の温度で加熱還流するか、常温で超音 波抽出する方法が挙げられる。抽出液は、濾過又は遠心分離等の適当な方法により 、不溶物を分離して粗抽出物を得ることができる。 [0037] As an extraction method, a method used for extraction of normal plant components can be used. Usually, 1 to 300 parts by mass of an organic solvent is used per 1 part by mass of a fresh or dried plant, and the mixture is heated to reflux at a temperature not higher than the boiling point of the solvent while stirring or shaking, or is subjected to ultrasonic extraction at room temperature. A method is mentioned. The crude extract can be obtained by separating the insoluble matter by an appropriate method such as filtration or centrifugation.
[0038] 抽出物は、各種クロマトグラフィー、例えば順相又は逆相のシリカゲルカラムクロマト グラフィ一により、精製することができる。順相シリカゲルカラムクロマトグラフィーにお いては、溶出溶媒としてクロ口ホルム Zメタノール混合液のグラジェントを用いると、ク ロロホルム:メタノール = 25 : 1程度で本発明の化合物が溶出される。また、逆相シリ 力ゲルカラムクロマトグラフィーにおいては、溶出溶媒としてへキサン Z酢酸ェチル混 合液 (4 : 1)を用いると、本発明の化合物は最初の方のフラクションとして溶出される。 [0038] The extract can be purified by various types of chromatography, for example, normal phase or reverse phase silica gel column chromatography. In normal phase silica gel column chromatography, when a gradient of Kuroguchi Form Z methanol mixture is used as an elution solvent, the compound of the present invention is eluted with about chloroform: methanol = 25: 1. In reverse-phase silica gel column chromatography, when a hexane / Zethyl acetate mixture (4: 1) is used as an elution solvent, the compound of the present invention is eluted as the first fraction.
[0039] 得られたフラクションは、さらに HPLC等により精製することができる。 [0039] The obtained fraction can be further purified by HPLC or the like.
また、本発明に用いる化合物は、化学的な合成法、又は、微生物又は酵素等を利
用した生物学的方法又は酵素的方法によって製造してもよい。 In addition, the compound used in the present invention can be obtained by a chemical synthesis method, a microorganism, an enzyme, or the like. It may be produced by a biological method or an enzymatic method used.
[0040] 上記のようにして得られる化合物又はそれを含む組成物力 本発明の化合物を含 むことは、例えば、マススペクトル法 (MS)及び核磁気共鳴スペクトル法 (NMR)等に よって確認することができる。 [0040] Compound obtained as described above or compositional power including the same The inclusion of the compound of the present invention is confirmed, for example, by mass spectrometry (MS), nuclear magnetic resonance spectroscopy (NMR), or the like. Can do.
[0041] 本発明の化合物は、脾臓機能改善作用、特に脾臓内分泌腺細胞の保護または脾 臓内分泌腺細胞の機能改善の作用を有する。脾臓機能改善作用、特に脾臓内分泌 腺細胞の保護または脾臓内分泌腺細胞の機能改善のための医薬または飲食品の 有効成分として使用することができる。尚、本発明において、脾臓内分泌腺細胞の保 護とは、脾臓内分泌腺細胞を種々の原因による変性カゝら保護すること、又は、脾臓内 分泌腺細胞のインスリン産生能が低下することを防止することを意味する。また、脾臓 内分泌腺細胞の機能改善とは、インスリン産生能が低下した脾臓内分泌腺細胞のィ ンスリン産生能を高めることを意味する。脾臓内分泌腺細胞の変性、又は脾臓内分 泌腺細胞の保護もしくは脾臓内分泌腺細胞の機能改善は、動物の脾臓組織切片の 顕微鏡観察もしくは血清中のインスリン量測定により評価が可能である。 [0041] The compound of the present invention has an effect of improving spleen function, in particular, protecting spleen endocrine cells or improving function of spleen endocrine cells. It can be used as an active ingredient of a medicine or food and drink for improving spleen function, particularly protecting spleen endocrine gland cells or improving function of spleen endocrine cells. In the present invention, protection of splenic endocrine cells means protecting splenic endocrine cells from degeneration caused by various causes, or preventing a decrease in the ability of splenic endocrine cells to produce insulin. means. In addition, improvement of the function of spleen endocrine gland cells means enhancement of insulin production capacity of spleen endocrine gland cells whose insulin production capacity has decreased. Degeneration of splenic endocrine cells, or protection of splenic endocrine cells or improvement of splenic endocrine cells can be evaluated by microscopic observation of a spleen tissue section of an animal or measurement of insulin in serum.
本発明の化合物は、上記作用を有する結果、脾臓内分泌腺細胞のインスリン産生 能の低下を防止し、又はインスリン産生能が低下した脾臓内分泌腺細胞のインスリン 産生能を高めることができる。 As a result of having the above-described action, the compound of the present invention can prevent a decrease in the insulin production ability of spleen endocrine gland cells, or can increase the insulin production ability of spleen endocrine gland cells having a reduced insulin production ability.
[0042] 後記実施例で使用した dbZdbマウスは、週齢が進むと共に脾臓の障害が見られる ことが知られている（Science, 153, 1127-1128, 1966)。このマウスに、抗酸化作用化 合物である N -ァセチル -L-システィン、ビタミン C及びビタミン Eを併用投与した 場合、脾臓中の j8細胞数の減少を一部予防できるとの報告があるが（Diabetes, 48, 2398-2406, 1999)、投与量は N—ァセチルー L—システィンだけでも 100gZ60kg であり、非常に大量の投与が必要となると予想される。それに対し、本願発明では、 低用量で脾臓内分泌腺細胞の保護または脾臓内分泌腺細胞の機能改善の作用を 発揮することが期待できる。 [0042] The dbZdb mice used in the examples described later are known to show spleen damage as they age (Science, 153, 1127-1128, 1966). Although it has been reported that the administration of N-acetyl-L-cystine, vitamin C and vitamin E, which are antioxidant compounds, can partially prevent a decrease in the number of j8 cells in the spleen. (Diabetes, 48, 2398-2406, 1999), N-acetylyl L-cystine alone is 100gZ60kg, and a very large dose is expected. On the other hand, the present invention can be expected to exert an effect of protecting the splenic endocrine cells or improving the function of the splenic endocrine cells at a low dose.
[0043] 本発明の医薬は、脾臓内分泌腺細胞の機能低下により引き起される疾患、例えば 、急性脾炎、慢性脾炎、 I型糖尿病、 Π型糖尿病における脾臓機能障害、老人性のィ ンスリン分泌低下に伴う脾臓機能低下症等の疾患の治療剤又は予防剤の有効成分
として使用することができる。また、本発明の化合物は、低毒性であることから、脾臓 癌治療において、抗腫瘍剤と併用することもできる。本発明の医薬は、好ましくは、ィ ンスリン産生能の低下に伴う疾患のうち、高血糖改善用として用いるものは除かれる [0043] The medicament of the present invention is a disease caused by a decrease in the function of splenic endocrine cells, such as acute splenitis, chronic splenitis, type I diabetes, splenic dysfunction in type 1 diabetes, senile insulin secretion. Active ingredient of therapeutic or preventive agent for diseases such as spleen hypofunction associated with decline Can be used as Further, since the compound of the present invention has low toxicity, it can be used in combination with an antitumor agent in the treatment of spleen cancer. The medicament of the present invention preferably excludes those used for improving hyperglycemia among diseases associated with decreased insulin production ability.
[0044] 尚、アロエベラの葉皮には、緩下作用を持つバルバロインやアロエェモジンが含ま れており、緩下作用を期待しない医薬又は飲食品としては、好ましくないと考えられ ている。したがって、本発明の化合物を含む組成物は、これらの成分が含まれていな いことが好ましい。また、アロエベラの葉肉又はその破砕物も、脾臓内分泌腺細胞の 保護または脾臓内分泌腺細胞の機能改善用の医薬の有効成分として用いることが できる。 [0044] It should be noted that the bark of aloe vera contains barbaroin and aloe emodin having a laxative action, and it is considered unpreferable as a medicine or food or drink that does not expect a laxative action. Accordingly, the composition containing the compound of the present invention preferably does not contain these components. Also, aloe vera mesophyll or a crushed product thereof can be used as an active ingredient of a medicine for protecting splenic endocrine cells or improving the function of splenic endocrine cells.
[0045] 本発明の化合物は、そのまま本発明の医薬または飲食品の有効成分として利用す ることが可能である。また、本発明の化合物を含む、植物の有機溶媒抽出物もしくは 熱水抽出物又はこれらの分画物（以下、「抽出物等」と呼ぶ)を医薬または飲食品の 有効成分として利用してもよい。この場合、医薬に含有させる前記抽出物等は、本発 明の化合物を、乾燥質量で 0. 001〜10質量％含んでいることが好ましぐ 0. 01〜1 質量％含んでいることがより好ましぐ 0. 05〜1質量0 /0含んでいることが特に好まし い。また、飲食品に含有させる前記抽出物等は、本発明の化合物を、乾燥質量で 0. 0001〜1質量％含んでいることが好ましぐ 0. 001〜1質量％含んでいることがより 好ましぐ 0. 005〜1質量％含んでいることが特に好ましい。前記抽出物等は、本発 明の化合物を 2種類以上含むものであってもよい。また、前記抽出物等は、溶液であ つてもよく、常法により凍結乾燥または噴霧乾燥して粉末として保存ないし使用するこ とちでさる。 [0045] The compound of the present invention can be used as it is as an active ingredient of the medicament or food or drink of the present invention. In addition, an organic solvent extract or hot water extract of a plant containing the compound of the present invention or a fraction thereof (hereinafter referred to as “extract etc.”) may be used as an active ingredient of a medicine or food and drink. Good. In this case, it is preferable that the extract or the like to be contained in a medicine contains 0.001 to 10% by mass of the compound of the present invention in terms of dry mass. it is not particularly preferred to contain more preferred instrument from 0.05 to 1 mass 0/0. Moreover, it is preferable that the said extract etc. contained in food-drinks contain 0.001 to 1 mass% of the compound of this invention by dry mass. It is more preferable to contain 0.001 to 1 mass%. It is particularly preferable to contain 0.005 to 1% by mass. The extract or the like may contain two or more compounds of the present invention. The extract or the like may be in the form of a solution, which may be stored or used as a powder after freeze-drying or spray-drying by a conventional method.
[0046] 本発明の医薬は、本発明の化合物又はそれを含む抽出物等の組成物をそのまま、 若しくはこれらを製剤学的に許容される製剤担体と組み合わせて、経口的、又は非 経口的にヒトを含む哺乳動物に投与することができる。尚、本発明の医薬において、 本発明の化合物は医薬に許容される塩にすることができる。医薬に許容可能な塩と して、金属塩 (無機塩)と有機塩との両方が含まれ、それらのリストは「レミントン'ファ ~~マシュ ~~アイカル，サイェンン' ~~ス Remington s Pharmaceutical Sciencesノ、第 1 /
版、第 1418ページ、 1985年」に掲載されているものが例示される。具体的には塩酸 塩、硫酸塩、リン酸塩、二リン酸塩、臭化水素酸塩および硫酸塩などの無機酸塩や、 リンゴ酸塩、マレイン酸塩、フマル酸塩、酒石酸塩、コハク酸塩、クェン酸塩、酢酸塩 、乳酸塩、メタンスルホン酸塩、 p—トルエンスルホン酸塩、パモ酸塩、サリチル酸塩 及びステアリン酸塩などの有機酸塩が非限定的に含まれる。また、ナトリウム、力リウ ム、カルシウム、マグネシウム、アルミニウム等の金属の塩、リジン等のアミノ酸との塩 とすることもできる。また、上記化合物もしくはその医薬上許容される塩の水和物等の 溶媒和物も本発明に含まれる。 [0046] The medicament of the present invention can be administered orally or parenterally by using the compound of the present invention or a composition such as an extract containing the same as it is or in combination with a pharmaceutically acceptable pharmaceutical carrier. It can be administered to mammals including humans. In the medicament of the present invention, the compound of the present invention can be converted to a pharmaceutically acceptable salt. Pharmaceutically acceptable salts include both metal salts (inorganic salts) and organic salts, a list of which is listed as “Remington's Fat ~~ Mash ~~ Ical, Sayen '~~ S Remingtons Pharmaceutical Sciences. No. 1 / Edition, page 1418, 1985 ”. Specifically, inorganic acid salts such as hydrochloride, sulfate, phosphate, diphosphate, hydrobromide and sulfate, malate, maleate, fumarate, tartrate, succinate Organic acids such as acid salts, citrates, acetates, lactates, methanesulfonates, p-toluenesulfonates, pamoates, salicylates and stearates are included without limitation. Further, it can be a salt of a metal such as sodium, strength rhodium, calcium, magnesium and aluminum, or a salt with an amino acid such as lysine. Further, solvates such as hydrates of the above compounds or pharmaceutically acceptable salts thereof are also included in the present invention.
[0047] 本発明の医薬の製剤形態は特に限定されず、治療目的に応じて適宜選択でき、具 体的には、錠剤、丸剤、散剤、液剤、懸濁剤、乳剤、顆粒剤、カプセル剤、シロップ 剤、坐剤、注射剤、軟膏剤、貼付剤、点眼剤、点鼻剤等を例示できる。製剤化にあた つては製剤担体として通常の脾臓等の内臓疾患の治療又は予防用の医薬に汎用さ れる賦形剤、結合剤、崩壊剤、滑沢剤、安定剤、矯味矯臭剤、希釈剤、界面活性剤 、注射剤用溶剤等の添加剤を使用できる。また、本発明の効果を損わない限り、本 発明の化合物又はそれを含む組成物と、他の脾臓疾患の治療又は予防作用を有す る薬剤とを併用してもよい。 [0047] The pharmaceutical preparation form of the present invention is not particularly limited and can be appropriately selected depending on the purpose of treatment. Specifically, tablets, pills, powders, solutions, suspensions, emulsions, granules, capsules Examples include suppositories, syrups, suppositories, injections, ointments, patches, eye drops, and nasal drops. For formulation, excipients, binders, disintegrants, lubricants, stabilizers, flavoring agents, diluting agents that are commonly used as pharmaceutical carriers for the treatment or prevention of normal visceral diseases such as spleen Additives such as agents, surfactants, and solvents for injections can be used. In addition, as long as the effects of the present invention are not impaired, the compound of the present invention or a composition containing the same may be used in combination with a drug having a therapeutic or prophylactic action for other spleen diseases.
[0048] 本発明の医薬中に含まれる本発明の化合物又はそれを含む組成物の量は、特に 限定されず適宜選択すればよいが、例えば、本発明の化合物の量として、製剤中に 0. 001〜10質量％、好ましくは 0. 01〜1質量。 /0、特に好ましくは 0. 05〜1質量％ とするのがよい。 [0048] The amount of the compound of the present invention or the composition containing the same contained in the medicament of the present invention is not particularly limited and may be appropriately selected. 001 to 10% by weight, preferably 0.01 to 1% by weight. / 0 , particularly preferably 0.05 to 1% by mass.
[0049] さらに、本発明の医薬は、脾臓内分泌腺細胞の機能低下に起因する種々の疾病 · 合併症等の予防、並びにこれら疾病'合併症等のリスクを低減することが可能である [0049] Furthermore, the medicament of the present invention is capable of preventing various diseases / complications caused by the reduced function of spleen endocrine cells and reducing the risk of these diseases' complications.
[0050] 力かる脾臓内分泌腺細胞の機能低下に起因する種々の疾病 ·合併症としては、神 経障害、腎症、網膜症、白内障、大血管障害、糖尿病等を例示することができる。 [0050] Examples of various diseases and complications resulting from the reduced function of splenic endocrine cells include neuropathy, nephropathy, retinopathy, cataract, macrovascular disorder, diabetes and the like.
[0051] 本発明の医薬の投与時期は特に限定されず、対象となる疾患の治療方法に従って 、適宜投与時期を選択することが可能である。また、投与形態は製剤形態、患者の 年齢、性別、その他の条件、患者の症状の程度等に応じて決定されることが好ましい
[0052] 本発明の医薬の有効成分の投与量は、用法、患者の年齢、性別、疾患の程度、そ の他の条件等により適宜選択される。通常有効成分としての本発明の化合物の量は 、好ましくは 0. 001〜50mgZkgZ曰、より好ましくは、 0. 01〜： LmgZkgZ曰での 範囲となる量を目安とするのが良い。また、本発明の化合物を含む組成物を用いる 場合は、組成物の乾燥重量として好ましくは 0. 1〜： LOOOmgZkgZ日、より好ましく は、 1〜： LOOmgZkgZ日となるような量を目安とするのが良い。いずれの場合も、 1 日 1回又は複数回に分けて投与することができる。 [0051] The administration time of the medicament of the present invention is not particularly limited, and can be appropriately selected according to the treatment method for the target disease. The dosage form is preferably determined according to the dosage form, the patient's age, sex, other conditions, the degree of symptoms of the patient, etc. [0052] The dose of the active ingredient of the medicament of the present invention is appropriately selected depending on the usage, patient age, sex, degree of disease, other conditions, and the like. Usually, the amount of the compound of the present invention as an active ingredient is preferably from 0.001 to 50 mgZkgZ 曰, more preferably from 0.01 to LmgZkgZ 曰. When a composition containing the compound of the present invention is used, the dry weight of the composition is preferably 0.1 to: LOOOmgZkgZ days, more preferably 1 to: LOOmgZkgZ days. Is good. In either case, it can be administered once or divided into several times a day.
[0053] 本発明の化合物又はそれを含む抽出物等は、飲食品 (飲料又は食品）に含有させ ることもできる。飲食品としては、前記有効成分の効果を損なわず、経口摂取できるも のであれば形態や性状は特に制限されず、前記有効成分を含有させること以外は、 通常飲食品に用いられる原料を用いて通常の方法によって製造することができる。 [0053] The compound of the present invention or an extract containing the compound may be contained in a food or drink (beverage or food). As the food and drink, the form and properties are not particularly limited as long as they can be taken orally without impairing the effect of the active ingredient, and using the raw materials usually used for food and drink, except for containing the active ingredient. It can be produced by a usual method.
[0054] 本発明の飲食品中に含まれる本発明の化合物又はそれを含む抽出物等の量は、 特に限定されず適宜選択すればよいが、例えば、本発明の化合物の量として、飲食 口 ¾中【こ 0. 0001〜1質量0/0、好まし<【ま0. 001〜1質量0/0、特【こ好まし<【ま0. 005〜 1質量0 /0とするのがよい。 [0054] The amount of the compound of the present invention or an extract containing the compound of the present invention contained in the food or drink of the present invention is not particularly limited and may be appropriately selected. For example, as the amount of the compound of the present invention, during ¾ [this 0.0001 to 1 mass 0/0, preferably <[or 0.001 to 1 mass 0/0, is given to the special [this preferably <[or 0.005 to 1 mass 0/0 Good.
[0055] 本発明の飲食品における用途としては、脾臓内分泌腺細胞の保護または脾臓内分 泌腺細胞の機能改善効果を利用するような種々の用途をとることが可能である。例え ば、「インスリン産生が低めの方」、「インスリンの働きが低めの方」、又は「脾臓の働き が気になる方」に適した飲食品、脾臓機能低下により引き起こされる糖尿病、及び過 度のアルコール摂取やストレスにより引き起こされる膝炎等の生活習慣病の危険要 因の低減 '除去に役立つ飲食品等の用途を例示することができる。 [0055] The food and drink of the present invention can be used for various purposes such as protecting splenic endocrine cells or improving the function of splenic secretory cells. For example, foods and drinks suitable for `` lower insulin production '', `` lower insulin function '', or `` spleen spleen function '', diabetes caused by reduced spleen function, and excessive Reduction of risk factors for lifestyle-related diseases such as knee inflammation caused by alcohol consumption and stress in foods' Uses such as food and drink that are useful for removal can be exemplified.
[0056] 尚、本発明の飲食品において、「脾臓内分泌腺細胞の保護または脾臓内分泌腺細 胞の機能改善」とは、脾臓内分泌腺細胞の機能低下に起因して導かれる種々の健 康への害を改善又は予防する事を意味しており、「ラ氏島機能保護」、「ラ氏島機能 改善」、「 細胞機能保護」、「 細胞機能改善」、「インスリン産生増強」、「インスリン 産生低下予防」、「インスリン作用増強」、「インスリン作用低下予防」等も、前記「脾臓 内分泌腺細胞の保護または脾臓内分泌腺細胞の機能改善」と同様の意味として、本
発明にお 、て例示することができる。 [0056] In the food and drink of the present invention, "protection of spleen endocrine gland cells or improvement of function of spleen endocrine gland cells" refers to various health damages caused by the reduced function of spleen endocrine gland cells. It is meant to improve or prevent `` La Isle Island Function Protection '', `` La Islet Island Function Improvement '', `` Cell Function Protection '', `` Cell Function Improvement '', `` Insulin Production Enhancement '', `` Insulin Production Decrease '' The terms “prevention”, “enhanced insulin action”, “prevention of decreased insulin action” and the like have the same meaning as “protection of splenic endocrine cells or improvement of function of splenic endocrine cells”. In the invention, it can be exemplified.
[0057] また、本発明の飲食品は、脾臓内分泌腺細胞の機能低下により引き起こされる疾 患、例えば急性脾炎、慢性脾炎、 I型糖尿病、 Π型糖尿病における脾臓機能障害、老 人性のインスリン分泌低下に伴う脾臓機能低下症等の疾患の予防に有用である。さ らに、本発明の飲食品は、脾臓内分泌腺細胞の機能低下に起因する種々の疾病 · 合併症等の予防、並びにこれら疾病'合併症等のリスクを低減することが可能である[0057] In addition, the food and drink of the present invention is a disease caused by a decrease in function of splenic endocrine cells, such as acute splenitis, chronic splenitis, type I diabetes, spleen dysfunction in type 2 diabetes, senile insulin secretion. It is useful for preventing diseases such as hyposplenic function associated with the decrease. Furthermore, the food and drink according to the present invention can prevent various diseases / complications caused by the reduced function of spleen endocrine gland cells and reduce the risk of these diseases' complications.
。また、本発明の化合物は、低毒性であることから、本発明の飲食品は、脾臓癌治療 にお 、て抗腫瘍剤を投与されて 、る患者にも有用である。 . Further, since the compound of the present invention has low toxicity, the food and drink of the present invention is also useful for patients who have been administered an antitumor agent in the treatment of spleen cancer.
[0058] 力かる脾臓内分泌腺細胞の機能低下に起因する種々の疾病 ·合併症としては、神 経障害、腎症、網膜症、白内障、大血管障害、糖尿病等を例示することができる。 [0058] Examples of various diseases and complications resulting from the decreased function of splenic endocrine cells include neuropathy, nephropathy, retinopathy, cataract, macrovascular disorder, diabetes and the like.
[0059] 本発明の飲食品は、脾臓内分泌腺細胞の保護または脾臓内分泌腺細胞の機能改 善のために用いられるものである旨の表示を付した飲食品、例えば「脾臓内分泌腺 細胞の保護または脾臓内分泌腺細胞の機能改善用と表示された、脾臓内分泌腺細 胞の保護または脾臓内分泌腺細胞の機能改善効果を有する化合物を含有する飲食 品」、あるいは「脾臓内分泌腺細胞の保護または脾臓内分泌腺細胞の機能改善用と 表示された、植物抽出物を含有する飲食品」、「脾臓内分泌腺細胞の保護または脾 臓内分泌腺細胞の機能改善用と記載された、アロエベラ抽出物を含有する飲食品」 、等として販売することが好ましい。 [0059] The food or drink of the present invention is a food or drink with an indication that it is used for protecting splenic endocrine cells or improving the function of splenic endocrine cells, for example, "protecting splenic endocrine cells or spleen" `` Food or drink containing a compound that has the effect of protecting splenic endocrine cells or improving splenic endocrine cells '' indicated to improve the function of endocrine cells, or `` protecting splenic endocrine cells or improving the function of splenic endocrine cells '' Food and drink containing plant extract labeled as "For food and drink containing aloe vera extract, described as protecting splenic endocrine cells or improving function of splenic endocrine cells", etc. It is preferable.
[0060] 尚、以上のような表示を行うために使用する文言は、「脾臓内分泌腺細胞の保護ま たは脾臓内分泌腺細胞の機能改善用」という文言のみに限られるわけではなぐそれ 以外の文言であっても、脾臓内分泌腺細胞を保護し、または機能低下を改善する効 果を表す文言であれば、本発明の範囲に包含されることはいうまでもない。そのよう な文言としては、例えば、需要者に対して、脾臓内分泌腺細胞を保護し、または機能 低下を改善する効果を認識させるような種々の用途に基づく表示も可能である。例え ば、「インスリン産生が低めの方に適した」、又は「インスリンの働きが低めの方に適し た」、「インスリン作用又はインスリン産生の低下により引き起こされる糖尿病、及び過 度のアルコール摂取やストレスにより引き起こされる膝炎等の生活習慣病の危険要 因（リスク)の低減'除去に役立つ」等の表示を例示することができる。
[0061] 前記「表示」とは、需要者に対して上記用途を知らしめるための全ての行為を意味 し、上記用途を想起，類推させうるような表示であれば、表示の目的、表示の内容、表 示する対象物'媒体等の如何に拘わらず、すべて本発明の「表示」に該当する。しか しながら、需要者が上記用途を直接的に認識できるような表現により表示することが 好ましい。具体的には、本発明の飲食品に係る商品又は商品の包装に上記用途を 記載する行為、商品又は商品の包装に上記用途を記載したものを譲渡し、引き渡し 、譲渡若しくは引渡しのために展示し、輸入する行為、商品に関する広告、価格表若 しくは取引書類に上記用途を記載して展示し、若しくは頒布し、又はこれらを内容と する情報に上記用途を記載して電磁気的 (インターネット等)方法により提供する行 為、等が例示できる。 [0060] It should be noted that the terminology used for the above indication is not limited to the term “for protecting splenic endocrine cells or improving the function of splenic endocrine cells”. Even if it is a word which expresses the effect which protects a spleen endocrine gland cell or improves functional decline, it cannot be overemphasized that it is included in the scope of the present invention. As such a wording, for example, it is possible to display based on various uses that allow the consumer to recognize the effect of protecting the splenic endocrine gland cells or improving the functional decline. For example, “suitable for those with lower insulin production” or “suitable for those with lower insulin activity”, “diabetes caused by reduced insulin action or insulin production, and excessive alcohol consumption and stress For example, it is possible to reduce the risk factor (risk) of lifestyle-related diseases such as kneeitis caused by [0061] The "display" means all acts for informing the consumer of the use, and if the display can recall and analogize the use, the purpose of the display, Regardless of the content, the object to be displayed, the medium, etc., all correspond to the “display” of the present invention. However, it is preferable to display it in such an expression that the consumer can directly recognize the use. Specifically, the act of describing the above-mentioned use in the product or the product packaging relating to the food or drink of the present invention, the product or the product packaging describing the above-mentioned use is transferred, and displayed for delivery, transfer or delivery Display or distribute the above uses in the acts of importing, advertisements on products, price lists or transaction documents, or distributing them, or describing the above uses in the contents of these information (such as the Internet) ) Examples of activities provided by the method.
[0062] 一方、表示としては、行政等によって認可された表示 (例えば、行政が定める各種 制度に基づいて認可を受け、そのような認可に基づいた態様で行う表示)であること が好ましぐ特に包装、容器、カタログ、パンフレット、 POP等の販売現場における宣 伝材、その他の書類等への表示が好ましい。 [0062] On the other hand, it is preferable that the display is a display approved by the government or the like (for example, a display that is approved based on various systems determined by the government and is performed in a manner based on such approval). In particular, it is preferable to display on materials such as packaging, containers, catalogs, pamphlets, POP, etc., and other documents.
[0063] また、例えば、健康食品、機能性食品、経腸栄養食品、特別用途食品、栄養機能 食品、医薬用部外品等としての表示を例示することができ、その他厚生労働省によつ て認可される表示、例えば、特定保健用食品、これに類似する制度にて認可される 表示を例示できる。後者の例としては、特定保健用食品としての表示、条件付き特定 保健用食品としての表示、身体の構造や機能に影響を与える旨の表示、疾病リスク 低減表示等を例示することができ、詳細にいえば、健康増進法施行規則 (平成 15年 4月 30日日本国厚生労働省令第 86号）に定められた特定保健用食品としての表示 (特に保健の用途の表示）、及びこれに類する表示が、典型的な例として列挙するこ とが可能である。 [0063] In addition, for example, indications such as health foods, functional foods, enteral nutritional foods, special-purpose foods, nutritional functional foods, quasi-drugs, etc. can be exemplified, and others by the Ministry of Health, Labor and Welfare Approved indications, for example, indications approved by foods for specified health use and similar systems can be exemplified. Examples of the latter include labeling as food for specified health use, labeling as conditionally specified food for specified health use, labeling that affects the structure and function of the body, labeling for reducing disease risk, etc. Speaking of health promotion law enforcement regulations (April 30, 2003 Ministry of Health, Labor and Welfare Ordinance No. 86) labeling as food for specified health use (especially labeling of health use), and similar The display can be listed as a typical example.
実施例 Example
[0064] 次に実施例を示して本発明を更に具体的に説明するが、本発明は以下の実施例 に限定されるものではない。 [0064] Next, the present invention will be described more specifically with reference to examples. However, the present invention is not limited to the following examples.
[0065] [製造例] [0065] [Production Example]
アロエベラの葉肉（透明ゲル部分） 100kgを、ホモジナイザーを用いて液状ィ匕し、こ
こに 100リットルの酢酸ェチル Zブタノール混合液 (3： 1)を添カロして攪拌した。 100 kg of aloe vera mesophyll (transparent gel part) is liquefied using a homogenizer. To this, 100 liters of ethyl acetate Z-butanol mixture (3: 1) was added and stirred.
[0066] ー晚放置した後、酢酸ェチル Zブタノール混合液と水層を分液して、酢酸ェチル[0066]-After leaving it to stand, the ethyl acetate Z-butanol mixed solution and the aqueous layer were separated to obtain ethyl acetate.
Zブタノール混合液を回収した。この酢酸ェチル Zブタノール混合液を減圧下濃縮 して得られた、酢酸ェチル Zブタノール混合液抽出物の重量は、 13. 5gであった。 シリカゲル 60 (メルク社製）を 400g充填しカラム〖こ、当該抽出物 13gを lmlのクロロホ ルム Zメタノール混合液（1： 1)に溶解させた溶液を通液してカラムに吸着させた後、 クロ口ホルム/メタノール混合液（クロ口ホルム：メタノール = 100 : 1、 25 : 1、 10 : 1、 5 ： 1及び 1： 1の各混合比）を使用し、メタノール濃度を段階的に上昇させるステップヮ ィズグラジェント法により溶出し、前記混合液の混合比毎に溶出液を分画した。これ らのフラクションのうち、クロ口ホルム：メタノール = 25 : 1で溶出してきたフラクションに 本発明の化合物が存在することを、順相及び逆相薄層クロマトグラフィー (メルク社製 、シリカゲノレ 60F254及び RP—18F2543)にて確認した。 The Z butanol mixture was recovered. The weight of the ethyl acetate Z butanol mixture extract obtained by concentrating the ethyl acetate Z butanol mixture under reduced pressure was 13.5 g. After 400 g of silica gel 60 (manufactured by Merck & Co., Ltd.) is packed, the column is packed and 13 g of the extract is dissolved in 1 ml of chloroform Z methanol mixture (1: 1) and adsorbed on the column. Increase the methanol concentration step-by-step using a mixture of Kuroguchi Form / Methanol (Kuroguchi Form: Methanol = 100: 1, 25: 1, 10: 1, 5: 1 and 1: 1). Elution was carried out by a stepwise gradient method, and the eluate was fractionated at each mixing ratio of the mixture. Among these fractions, the presence of the compound of the present invention in the fraction eluted with chloroform: methanol = 25: 1 indicates that the compound of the present invention exists in normal phase and reverse phase thin layer chromatography (Merck, Silica Genore 60F254 and RP —18F2543).
[0067] この本発明の化合物を含む、粗精製物質 (粗精製物 1)は 3gであった。また、このと き得られた、クロ口ホルム：メタノール = 10 : 1および、 1 : 1で溶出されたフラクションの 粗精製物収量は、それぞれ 1. 17g及び、 2. 27gであった。これらのフラクションの溶 媒を除去した後、それぞれの抽出物を lmlのクロ口ホルム Zメタノール混合液（1： 1) に溶解し、シリカゲル 60を 100g充填したカラムに通液してカラムに吸着させた後、へ キサン Z酢酸ヱチル混合液 (4 : 1) 1100mlで溶出した。溶出フラクションを、順に 30 0ml (フラクション A)、 300ml (フラクション B)、 500ml (フラクション C)ずつ分取した。 それぞれのフラクションの溶媒除去後の収量は、フラクション A : 0. 6g、フラクション B : 1. 35g、フラクション C : 0. 15gであった。 [0067] The crudely purified material (crude product 1) containing the compound of the present invention was 3 g. In addition, the crude product yields of the fractions eluted with chloroform-form: methanol = 10: 1 and 1: 1 obtained at this time were 1.17 g and 2.27 g, respectively. After removing the solvent of these fractions, each extract was dissolved in 1 ml of Kloform-form Z methanol mixture (1: 1), passed through a column packed with 100 g of silica gel 60 and adsorbed on the column. After that, elution was performed with 1100 ml of hexane Z acetyl acetate mixture (4: 1). The elution fraction was fractionated in order of 300 ml (fraction A), 300 ml (fraction B), and 500 ml (fraction C). The yield of each fraction after removal of the solvent was fraction A: 0.6 g, fraction B: 1.35 g, and fraction C: 0.15 g.
[0068] 本発明の化合物が、フラクション A (粗精製物 2)に濃縮されたことを、順相及び逆相 薄層クロマトグラフィーにて確認した。この粗精製物 2を、さらに、コスモシール C18 ( ナカライテスタ社製)を装着した HPLCを用いて、クロ口ホルム/へキサン混合液 (85 ： 15)にて分離し、化合物 3 (4—メチルコレスト 7 ェンー 3 オール）、化合物 4 (4 メチルエルゴストー 7—ェン 3—オール）、化合物 5 (4—メチルスチグマストー 7— ェン 3 オール）を、それぞれ 1. 3mg、 1. 2mg、 lmg得た。各々の化合物の構造 は MSおよび NMRにて確認した。
[0069] 〔試験例 1〕 [0068] It was confirmed by normal phase and reverse phase thin layer chromatography that the compound of the present invention was concentrated in fraction A (crude product 2). The crude purified product 2 was further separated with a mixed solution of formaldehyde / hexane (85:15) using HPLC equipped with Cosmosil C18 (manufactured by Nakarai Testa Co.) to give compound 3 (4-methylcholest 7 mg 3 ol), compound 4 (4 methyl ergostost 7-en 3 ol), compound 5 (4-methyl stigmasto 7-en 3 ol), 1.3 mg, 1.2 mg and lmg, respectively. Obtained. The structure of each compound was confirmed by MS and NMR. [Test Example 1]
本試験は、脾臓機能低下また脾臓組織障害のモデル動物として知られて ヽる dbZ dbマウスを用いて、口フエノール骨格を持つ化合物の内分泌細胞の機能 (インスリン 産生能)の保護作用を評価するために行った。 The purpose of this study is to evaluate the protective effect of endocrine cell function (insulin-producing ability) of compounds with oral phenol skeleton using dbZ db mice, which are known as model animals for spleen hypofunction or spleen tissue damage. Went to.
[0070] (1)試料の調製 [0070] (1) Sample preparation
前記製造例で製造した 4 メチルコレスト 7 ェン 3 オールを試験試料 1、 4 ーメチルエルゴスト— 7 ェン 3 オールを試験試料 2、及び 4ーメチルスチグマス トー 7—ェン— 3—オールを試験試料 3とした。 Test sample 1, 4-methyl cholest 7-en 3 ol produced in the above production example, test sample 2, 4-methyl ergost-7-en 3 ol, test sample 2, and 4-methyl stigmasto 7-en 3-ol Was designated as test sample 3.
[0071] (2)試験方法 [0071] (2) Test method
本試験にお!、てマウスは 6週齢、雄性 dbZdbマウス（日本クレア社より購入)を使用 した。前記マウスを 1群 7匹に群分けした。各試験試料を DMSOに溶解した後、生理 食塩水にて、 0. 1または Ι /z gZmlに調整した。最終 DMSO濃度は、 0. 2%に調整 した。該脾臓障害モデルマウスに各々 1mlずつ、 1日 1回、ゾンデを用いて経口投与 を 42日間連続で行った。連続投与 43日目に血清中のインスリン量を、レビスインスリ ンマウス ELISAキット（シバヤギ社製）を用いて測定した。 In this study, 6-week-old male dbZdb mice (purchased from Claire Japan) were used. The mice were divided into 7 groups per group. Each test sample was dissolved in DMSO and then adjusted to 0.1 or Ι / z gZml with physiological saline. The final DMSO concentration was adjusted to 0.2%. One ml each of the spleen disorder model mice was orally administered once a day using a sonde for 42 consecutive days. On day 43 of continuous administration, the amount of insulin in the serum was measured using a Levis Insulin Mouse ELISA kit (manufactured by Shibayagi).
[0072] (3)試験結果 [0072] (3) Test results
試料連続投与 43日目の血清中インスリン量を表 1に示す。試験試料 1、試験試料 2 または試験試料 3を 1 μ gZ匹の濃度で投与した場合、血清中インスリン量は、それ ぞれ陰性試料の 184%、 210%および 211%と高ぐ脾臓障害保護による脾臓機能 (インスリン産生能)の保護効果が見られた。一方、 0. 1 gZ匹の濃度で投与した場 合、有意な脾臓機能の保護効果は見られな力 た。また、投与期間中、体重および 病理的な所見からも副作用は全くみられな力つた。 Table 1 shows the amount of insulin in serum on day 43 of continuous sample administration. When test sample 1, test sample 2 or test sample 3 is administered at a concentration of 1 μgZ, the serum insulin level is 184%, 210% and 211% of the negative sample, respectively, due to protection against spleen damage A protective effect on spleen function (insulin production ability) was observed. On the other hand, when administered at a concentration of 0.1 gZ, no significant protective effect on spleen function was observed. During the administration period, no side effects were seen from the weight and pathological findings.
[0073] [表 1]
表 1 連続投与 43日目の血清中のインスリン量 [0073] [Table 1] Table 1 Insulin levels in serum on day 43 of continuous administration
投与 43日目 Day 43 of administration
aii料 く陰性試料に対する 値> aii Values for negative samples>
血中インスリン量（ng/ml) Blood insulin level (ng / ml)
陰性試料 1.99 + 0.66 Negative sample 1.99 + 0.66
試験試料 1 (l s) 3.67 + 0.80 <0.003*> Test sample 1 (l s) 3.67 + 0.80 <0.003 *>
試験試料 1 (0. g) 2.33 i 1.23 <0.19> Test sample 1 (0.g) 2.33 i 1.23 <0.19>
試験試料 2 ( g) 4.17土 2.23 <0.04*> Test sample 2 (g) 4.17 Sat 2.23 <0.04 *>
試験試料 2 (O.l g) 2.32 + 1.52 <0.27> Test sample 2 (O.l g) 2.32 + 1.52 <0.27>
験試料 ύ ( g) 4.20 + 1.86 <0.02*> Test sample ύ (g) 4.20 + 1.86 <0.02 *>
試験試料 3 (0. g) 2.23 + 0.68 <0.17> Test sample 3 (0.g) 2.23 + 0.68 <0.17>
* ：統計学的に有意差があることを示す。 *: Indicates that there is a statistically significant difference.
[0074] 〔試験例 2〕 [0074] [Test Example 2]
本試験は、脾臓機能低下また脾臓組織障害のモデル動物として知られて ヽる dbZ dbマウスを用いて、口フエノール骨格を持つ化合物の脾臓組織保護作用につ ヽて検 This study examined the protective effect of compounds with oral phenolic skeleton on the spleen tissue using dbZ db mice, which are known as model animals for spleen hypofunction and spleen tissue disorders.
B、Jした。 B, J.
[0075] (1)試料の調製 [0075] (1) Sample preparation
前記製造例で製造した 4 メチルコレスト 7 ェン 3 オールを試験試料 1、 4 ーメチルエルゴスト— 7 ェン 3 オールを試験試料 2、及び 4ーメチルスチグマス トー 7—ェン— 3—オールを試験試料 3とした。また、 /3—シトステロール (タマ生化学 社製)を対照試料として使用した。 Test sample 1, 4-methyl cholest 7-en 3 ol produced in the above production example, test sample 2, 4-methyl ergost-7-en 3 ol, test sample 2, and 4-methyl stigmasto 7-en 3-ol Was designated as test sample 3. Moreover, / 3-sitosterol (manufactured by Tama Seikagaku) was used as a control sample.
[0076] (2)試験方法 [0076] (2) Test method
本試験にお!、てマウスは 6週齢、雄性 dbZdbマウス（日本クレア社より購入)を使用 した。前記マウスを 1群 7匹に群分けした。各試験試料を DMSOに溶解した後、生理 食塩水にて、 1 gZmlに調整した。最終 DMSO濃度は、 0. 2%に調整した。モデ ルマウスに各々 1mlずつ、 1日 1回、ゾンデを用いて経口投与を 42日間連続で行つ た。連続投与 43日目に脾臓を摘出し、十二指腸側から上流、中流、下流の 3部分に 分け、ホルマリン液にて固定した後、常法に従いパラフィンブロックを作製した。パラ フィンブロックより切片スライドを作製し、へマトキシリン—ェォジン染色を行った。脾 臓 3箇所の切片上に存在するラ氏島の数及び、切片中の最大面積を有するラ氏島 の面積を、顕微鏡（ニコン社製「ECLIPSE E600」）の接眼マイクロメーターを用いて測 し 7こ。
[0077] (3)試験結果 In this study, 6-week-old male dbZdb mice (purchased from Claire Japan) were used. The mice were divided into 7 groups per group. Each test sample was dissolved in DMSO and then adjusted to 1 gZml with physiological saline. The final DMSO concentration was adjusted to 0.2%. Each model mouse was orally administered once a day using a sonde for 1 day, 42 ml for 42 days. On day 43 of continuous administration, the spleen was removed, divided into three parts upstream, midstream, and downstream from the duodenum side, fixed with formalin solution, and a paraffin block was prepared according to a conventional method. Section slides were prepared from paraffin blocks and stained with hematoxylin-eosin. Using the eyepiece micrometer of the microscope (Nikon Corporation “ECLIPSE E600”), measure the number of La Isles present on the three sections of the spleen and the area of La Islet that has the largest area in the section. 7 [0077] (3) Test results
試料連続投与 43日目における、膝臓切片中のラ氏島数を表 2に、ラ氏島の最大面 積を表 3に示す。試験試料 1、試験試料 2または試験試料 3を投与したマウスにおい て、脾臓でのラ氏島の数は、それぞれ陰性試料投与マウスにおけるラ氏島数の 188 %、 159%および 150%となり、明らかに多いことがわ力つた。同様に、試験試料 1ま たは試験試料 2を投与したマウスにおいて、ラ氏島の最大面積は、それぞれ陰性試 料の 3.6倍、 4倍および 2.8倍の大きさを保っており、脾臓障害によるラ氏島の縮小 を予防していることがわかった。一方、対照試料を投与したマウスでは、ラ氏島の数 及び最大面積において差は見られず、脾臓組織保護効果を示さなかった。これらの 結果より、 4ーメチルコレスト 7—ェンー3—オール、 4ーメチルエルゴスト— 7—ェン 3—オール、及び 4ーメチルスチグマストー 7—ェンー3—オールは、脾臓組織、特 に内分泌細胞の保護作用を有することが明らかになった。 Table 2 shows the number of la isles in the knee slices on the 43rd day of continuous sample administration, and Table 3 shows the maximum area of la isles. In mice that received test sample 1, test sample 2, or test sample 3, the number of la islets in the spleen was 188%, 159%, and 150% of the number of la islets in the negative sample-treated mice, respectively. There was a lot of power in this. Similarly, in mice that received test sample 1 or test sample 2, the maximum area of La Islet was 3.6 times, 4 times, and 2.8 times that of the negative sample, respectively. It turned out to be preventing the reduction of La Island. On the other hand, in the mice administered with the control sample, there was no difference in the number and the maximum area of La Islet, and the spleen tissue protective effect was not shown. From these results, 4-methylcholest 7-en-3-ol, 4-methylergost 7-en 3-ol, and 4-methyl stigmast 7-en 3-ol are spleen tissues, especially endocrine cells. It became clear that it has a protective effect.
[0078] [表 2] 表 2 投与マウスにおける、 降臓病理切片中のラ氏島の数 [0078] [Table 2] Table 2 Number of La Islets in fallen pathological sections in mice treated
投与 43日目 Day 43 of administration
試料 く陰性試料に対する 値> Sample Value for negative sample>
切片中のラ氏島の数 (個） Number of La Island in section (pieces)
陰性試料 40.3土 9.7 Negative sample 40.3 Sat 9.7
試験試料 1 (l g) 75.7土 24.7 <0.008*> Test sample 1 (l g) 75.7 Sat 24.7 <0.008 *>
試験試料 2 (l g) 64.1土 9.1 <0.0003*> Test sample 2 (l g) 64.1 Sat 9.1 <0.0003 *>
試験試料 3 (l g) 60.41 11.6 <0.004*> Test sample 3 (l g) 60.41 11.6 <0.004 *>
対照試料 （1/zg) 42.3土 20.1 <0.8> Control sample (1 / zg) 42.3 Sat 20.1 <0.8>
* ：統計学的に有意差があることを示す。 *: Indicates that there is a statistically significant difference.
[0079] [表 3] 表 3 投与マウスにおける、 塍臓病理切片中のラ氏島の最大面積 ラ氏島の投最与大 4面3積日^ く陰性試料に対する 〉 陰性試験 44.5 ± 17.7 [0079] [Table 3] Table 3 Largest area of La Island in the spleen pathological section in mice treated with La Fore Island for the largest 4 surfaces, 3 days, and negative samples> Negative test 44.5 ± 17.7
試験試料 1 d g) 160.0土 116.0 <0.04*> Test sample 1 d g) 160.0 Sat 116.0 <0.04 *>
Βιΐ験試料 2 d g) 178.7土 143.4 <0.005*> 試 料 ιΐ Test sample 2 d g) 178.7 Sat 143.4 <0.005 *>
S式験試料 3 (l g) 122.6土 51.4 <0.006*> S-type test sample 3 (l g) 122.6 Sat 51.4 <0.006 *>
対照試料 d g) 69.1 土 40.6 <0.18> Control sample d g) 69.1 Sat 40.6 <0.18>
* ：統計学的に有意差があることを示す。
産業上の利用可能性 *: Indicates that there is a statistically significant difference. Industrial applicability
本発明の医薬及び飲食品は、安全に投与又は摂取でき、かつ、脾臓内分泌腺細 胞を保護し、機能を改善する作用を持つ。また、本発明の医薬及び飲食品の有効成 分は、食経験上安全に摂取でき、入手容易である植物、例えばアロエベラ (Aloe bar badensis Miller)等のユリ科植物力も製造することができる。
The medicament and food and drink of the present invention can be safely administered or ingested, and have an action of protecting spleen endocrine cells and improving function. In addition, the active ingredients of the medicament and food and drink of the present invention can also be produced as a plant that can be safely ingested and easily obtained, for example, a plant of Liliaceae such as Aloe bar badensis Miller.
Claims
請求の範囲 The scope of the claims
下記の一般式 (1)で表される化合物を有効成分として含む、脾臓機能改善のため の医薬。 A medicament for improving spleen function, comprising a compound represented by the following general formula (1) as an active ingredient.
[化 1] [Chemical 1]
R2 R3 R2 R3
(式中、 R1は、炭素原子数 6〜16の直鎖状または分枝鎖状のアルキル基であり、 2 重結合を全く含まないか、又は、 1つもしくは 2つ含んでいてもよぐヒドロキシル基お よび Z又はカルボ-ル基を含んでいてもよぐ R2、 R3は各々独立に水素原子、炭素 原子数 1〜3のアルキル基、又は置換アルキル基であり、 R4は環を構成する炭素原 子とともに C = 0を形成する力、または、 OH、 -OCOCHのいずれかである。 ) (In the formula, R1 is a linear or branched alkyl group having 6 to 16 carbon atoms and does not contain any double bond, or may contain one or two. R2 and R3 may each independently contain a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or a substituted alkyl group, and R4 constitutes a ring. This is the force that forms C = 0 with carbon atoms, or OH or -OCOCH.)
3 Three
[2] 脾臓機能改善が、脾臓内分泌腺細胞の保護又は脾臓内分泌腺細胞の機能改善 である請求項 1に記載の医薬。 [2] The medicament according to claim 1, wherein the improvement of spleen function is protection of spleen endocrine cells or improvement of function of spleen endocrine cells.
[3] 前記 R2及び R3の一方が水素原子であり、他方力メチル基であり、 R4が水酸基で ある、請求項 1又は 2に記載の医薬。 [3] The medicament according to claim 1 or 2, wherein one of R2 and R3 is a hydrogen atom, the other is a methyl group, and R4 is a hydroxyl group.
[4] 前記 R1が下記式の!/、ずれかで表される請求項 3に記載の医薬。 [4] The medicament according to claim 3, wherein R1 is represented by! / Or a deviation of the following formula.
[化 2] [Chemical 2]
-CH2-CH2-CH (一 CH2 - CH3) -CH (CH3) 2 -CH 2 -CH 2 -CH (One CH 2 -CH 3 ) -CH (CH 3 ) 2
— CH2— CH2— CH = C (CH3) 2 — CH 2 — CH 2 — CH = C (CH 3 ) 2
一 CH2— CH = C (CH 3) — CH (CH3) 2 CH 2 — CH = C (CH 3 ) — CH (CH 3 ) 2
— CH2 - CH2 - C (=CH-CH3) — CH (CH3) 2 — CH 2 -CH 2 -C (= CH-CH 3 ) — CH (CH 3 ) 2
-CH2-CH2-CH (R a) =C (CH3) R b -CH 2 -CH 2 -CH (R a) = C (CH 3 ) R b
(ただし、 R a、 R bは、 — H、 -OH. 又は一 C H 3のいずれかである。 ） 一 CH2 - CH2 - CH (R c) 一 CH (CH3) R d (However, R a and R b are either —H, —OH. Or one CH 3. ) One CH 2 —CH 2 —CH (R c) One CH (CH 3 ) R d
(ただし、 R c、 Rdは、 一 H、 _OH、 又は一 CH 3のいずれかである。 ）
[5] 前記化合物が、 4ーメチルコレストー7—ェンー3—オール、 4ーメチルエルゴスト— 7—ェン 3—オール、及び 4 メチルスチグマスト 7—ェン 3—オールからなる 群力 選ばれる請求項 4に記載の医薬。 (However, R c and Rd are either 1 H, _OH, or 1 CH 3. ) [5] The compound is composed of 4-methylcholest-7-en-3-ol, 4-methylergost-7-en-3-ol, and 4-methylstigmast 7-en 3-ol. The medicament according to claim 4, which is selected.
[6] 前記化合物を乾燥質量で 0. 001〜： L0質量％含む請求項 1〜5のいずれか一項に 記載の医薬。 [6] The medicament according to any one of [1] to [5], comprising the compound in a dry mass of from 0.001 to L0% by mass.
[7] 下記一般式（1)で表される化合物を含む植物の有機溶媒抽出物もしくは熱水抽出 物又はこれらの分画物であって、前記化合物を乾燥重量で 0. 001〜： L0質量％含む 組成物を有効成分として含む、脾臓機能改善のための医薬。 [7] An organic solvent extract or hot water extract of a plant containing the compound represented by the following general formula (1), or a fraction thereof, wherein the compound is in a dry weight of 0.001 to L0 mass. A medicament for improving spleen function, comprising the composition as an active ingredient.
(式中、 R1は、炭素原子数 6〜16の直鎖状または分枝鎖状のアルキル基であり、 2 重結合を全く含まないか、又は、 1つもしくは 2つ含んでいてもよぐヒドロキシル基お よび Z又はカルボ-ル基を含んでいてもよぐ R2、 R3は各々独立に水素原子、炭素 原子数 1〜3のアルキル基、又は置換アルキル基であり、 R4は環を構成する炭素原 子とともに C = 0を形成する力、または、 OH、 -OCOCHのいずれかである。 ) (In the formula, R1 is a linear or branched alkyl group having 6 to 16 carbon atoms and does not contain any double bond, or may contain one or two. R2 and R3 may each independently contain a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or a substituted alkyl group, and R4 constitutes a ring. This is the force that forms C = 0 with carbon atoms, or OH or -OCOCH.)
3 Three
[8] 脾臓機能改善が、脾臓内分泌腺細胞の保護又は脾臓内分泌腺細胞の機能改善 である請求項 7に記載の医薬。 [8] The medicament according to claim 7, wherein the improvement of spleen function is protection of spleen endocrine cells or improvement of function of spleen endocrine cells.
[9] 前記植物がユリ科の植物である、請求項 7又は 8に記載の医薬。 [9] The medicament according to claim 7 or 8, wherein the plant is a lily family plant.
[10] 前記ユリ科植物がアロエ属に分類される植物である、請求項 9に記載の医薬。 10. The medicament according to claim 9, wherein the lily family plant is a plant classified into the genus Aloe.
[11] 下記の一般式 (1)で示すィ匕合物を有効成分として含む、脾臓機能改善のための飲 [11] A drink for improving spleen function, which contains a compound represented by the following general formula (1) as an active ingredient
^ P ^ P
[化 4]
[Chemical 4]
(式中、 R1は、炭素原子数 6〜16の直鎖状または分枝鎖状のアルキル基であり、 2 重結合を全く含まないか、又は、 1つもしくは 2つ含んでいてもよぐヒドロキシル基お よび Z又はカルボ-ル基を含んでいてもよぐ R2、 R3は各々独立に水素原子、炭素 原子数 1〜3のアルキル基、又は置換アルキル基であり、 R4は環を構成する炭素原 子とともに C = 0を形成する力、または、 OH、 -OCOCHのいずれかである。 ) (In the formula, R1 is a linear or branched alkyl group having 6 to 16 carbon atoms and does not contain any double bond, or may contain one or two. R2 and R3 may each independently contain a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or a substituted alkyl group, and R4 constitutes a ring. This is the force that forms C = 0 with carbon atoms, or OH or -OCOCH.)
3 Three
脾臓機能改善が、脾臓内分泌腺細胞の保護又は脾臓内分泌腺細胞の機能改善 である請求項 11に記載の飲食品。 12. The food or drink according to claim 11, wherein the improvement of spleen function is protection of spleen endocrine cells or improvement of function of spleen endocrine cells.
前記 R2及び R3の一方が水素原子であり、他方力メチル基であり、 R4が水酸基で ある、請求項 11又は 12に記載の飲食品。 13. The food or drink according to claim 11 or 12, wherein one of R2 and R3 is a hydrogen atom, the other is a force methyl group, and R4 is a hydroxyl group.
前記 R1が下記式のいずれかで表される請求項 13に記載の飲食品。 The food or drink according to claim 13, wherein R1 is represented by any of the following formulae.
[化 5] [Chemical 5]
-CH2-CH2-CH (-CH2-CH3) -CH (CH3) 2 -CH 2 -CH 2 -CH (-CH2-CH3) -CH (CH 3 ) 2
-CH2-CH2-CH = C (C H 3) 2 -CH 2 -CH 2 -CH = C (CH 3 ) 2
-CH2-CH = C (CH 3) — CH (CH3) 2 -CH 2 -CH = C (CH 3 ) — CH (CH 3 ) 2
-CH2-CH2-C (=CH-CH3) — CH (CH3) a -CH 2 -CH 2 -C (= CH-CH 3 ) — CH (CH 3 ) a
-CH2-CH2-CH (R a) =C (CH 3) R b -CH 2 -CH 2 -CH (R a) = C (CH 3 ) R b
(ただし、 R a、 R bは 一 H、 -OH, 又は一 C H 3のいずれかである。 ） — CH2 - CH2 - CH (R c) — CH (CH3) Rd (Wherein, R a, are R b is one H, -OH, or any one CH 3.) - CH 2 - CH 2 - CH (R c) - CH (CH 3) Rd
(ただし、 R c、 R dは、 一 H、 _OH、 又は— CH 3のいずれかである。 ） 前記化合物が、 4ーメチルコレストー7—ェンー3—オール、 4ーメチルエルゴスト— 7—ェン 3—オール、及び 4 メチルスチグマスト 7—ェン 3—オールからなる 群から選ばれる、請求項 14に記載の飲食品。 (However, R c and R d are either H, _OH, or —CH 3. ) The compound is 4-methylcholest-7-en-3-ol, 4-methylergost 7— 15. The food or drink according to claim 14, which is selected from the group consisting of: 3-ol and 4-methylstigmast 7-en-3-ol.
前記化合物を乾燥質量で 0.0001〜1質量％含む請求項 11〜15のいずれか一
項に記載の飲食品。 The compound according to any one of claims 11 to 15, comprising 0.0001 to 1% by mass of the compound in terms of dry mass. Food / beverage products of description.
下記一般式（1)で表される化合物を含む植物の有機溶媒抽出物もしくは熱水抽出 物又はこれらの分画物であって、前記化合物を乾燥重量で 0. 0001〜1質量％含む 組成物を有効成分として含む、脾臓機能改善のための飲食品。 An organic solvent extract or hot water extract of a plant containing a compound represented by the following general formula (1) or a fraction thereof, comprising 0.001 to 1% by mass of the compound by dry weight Foods and drinks for improving spleen function, containing as an active ingredient.
[化 6] [Chemical 6]
R2 R3 R2 R3
(式中、 R1は、炭素原子数 6〜16の直鎖状または分枝鎖状のアルキル基であり、 2 重結合を全く含まないか、又は、 1つもしくは 2つ含んでいてもよぐヒドロキシル基お よび Z又はカルボ-ル基を含んでいてもよぐ R2、 R3は各々独立に水素原子、炭素 原子数 1〜3のアルキル基、又は置換アルキル基であり、 R4は環を構成する炭素原 子とともに C = 0を形成する力、または、 OH、 -OCOCHのいずれかである。 ) (In the formula, R1 is a linear or branched alkyl group having 6 to 16 carbon atoms and does not contain any double bond, or may contain one or two. R2 and R3 may each independently contain a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or a substituted alkyl group, and R4 constitutes a ring. This is the force that forms C = 0 with carbon atoms, or OH or -OCOCH.)
3 Three
[18] 脾臓機能改善が、脾臓内分泌腺細胞の保護又は脾臓内分泌腺細胞の機能改善 である請求項 17に記載の飲食品。 [18] The food or drink according to claim 17, wherein the improvement of spleen function is protection of spleen endocrine cells or improvement of function of spleen endocrine cells.
[19] 前記植物がユリ科の植物である、請求項 17又は 18に記載の飲食品。 [19] The food or drink according to claim 17 or 18, wherein the plant is a lily family plant.
[20] 前記ユリ科植物がアロエ属に分類される植物である、請求項 19に記載の飲食品。 20. The food or drink according to claim 19, wherein the lily family plant is a plant classified as Aloe.
[21] 脾臓機能改善のために用いられる旨の表示を付した、請求項 11〜20のいずれか 一項に記載の飲食品。 [21] The food or drink according to any one of claims 11 to 20, which is labeled to be used for improving spleen function.
[22] 脾臓機能改善用の医薬の製造における、下記化学式（1)に示される構造をもつ化 合物又はそれを含む組成物の使用。 [22] Use of a compound having a structure represented by the following chemical formula (1) or a composition comprising the same in the manufacture of a medicament for improving spleen function.
[化 7]
[Chemical 7]
R2 R3 R2 R3
[23] 脾臓機能改善が、脾臓内分泌腺細胞の保護又は脾臓内分泌腺細胞の機能改善 である請求項 22に記載の使用。 [23] The use according to claim 22, wherein the improvement of spleen function is protection of spleen endocrine cells or improvement of function of spleen endocrine cells.
[24] 前記組成物が、前記化合物を乾燥質量で 0. 001〜10質量％含むユリ科植物の 抽出物又はその分画物である、請求項 22又は 23に記載の使用。 [24] The use according to claim 22 or 23, wherein the composition is a lily family extract or a fraction thereof containing 0.001 to 10% by mass of the compound in a dry mass.
[25] 脾臓の機能改善をする方法であって、下記化学式（1)に示される構造をもつ化合 物又はそれを含む組成物を、脾臓の機能改善をしょうとする対象に投与することを特 徴とする方法。 [25] A method for improving spleen function, comprising administering a compound having the structure represented by the following chemical formula (1) or a composition comprising the same to a subject who intends to improve spleen function: How to make a sign.
[化 8] [Chemical 8]
R2 R3 脾臓の機能改善が、脾臓内分泌腺細胞の保護又は脾臓内分泌腺細胞の機能改 善である請求項 25に記載の方法。 26. The method according to claim 25, wherein the functional improvement of R2 R3 spleen is protection of splenic endocrine cells or functional improvement of splenic endocrine cells.
前記組成物が、前記化合物を乾燥質量で 0. 001〜10質量％含むユリ科植物の 抽出物又はその分画物である、請求項 25又は 26に記載の方法。
27. The method according to claim 25 or 26, wherein the composition is a lily family extract or a fraction thereof containing 0.001 to 10% by mass of the compound in a dry mass.
Priority Applications (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2007516211A JP4065017B2 (en) | 2005-05-17 | 2006-02-28 | Medicine or food and drink for improving pancreatic function |
| CA2584974A CA2584974C (en) | 2005-05-17 | 2006-02-28 | Drug and food or drink for improving pancreatic functions |
| CN2006800023914A CN101102777B (en) | 2005-05-17 | 2006-02-28 | Medicines, food, or drink to improve pancreas function |
| EP06714846.0A EP1808175B1 (en) | 2005-05-17 | 2006-02-28 | Drug and food or drink for improving pancreatic functions |
| US11/576,652 US8101594B2 (en) | 2005-05-17 | 2006-02-28 | Method for improving pancreatic functions |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2005-144385 | 2005-05-17 | ||
| JP2005144385 | 2005-05-17 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2006123465A1 true WO2006123465A1 (en) | 2006-11-23 |
Family
ID=37431047
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/JP2006/303709 WO2006123465A1 (en) | 2005-05-17 | 2006-02-28 | Drugs, food or drink for improving pancreatic functions |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US8101594B2 (en) |
| EP (1) | EP1808175B1 (en) |
| JP (1) | JP4065017B2 (en) |
| KR (2) | KR20070063574A (en) |
| CN (1) | CN101102777B (en) |
| CA (1) | CA2584974C (en) |
| RU (1) | RU2351340C2 (en) |
| WO (1) | WO2006123465A1 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007034851A1 (en) * | 2005-09-22 | 2007-03-29 | Morinaga Milk Industry Co., Ltd. | Visceral fat accumulation inhibitor |
| JP2011046708A (en) * | 2009-08-28 | 2011-03-10 | Sinphar Tian-Li (Hangzhou) Pharmaceutical Co Ltd | Use of lanostane and poria extract in treating diabetes |
| WO2023054477A1 (en) * | 2021-09-28 | 2023-04-06 | 森永乳業株式会社 | Method for producing aloe extract |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2548811C (en) * | 2004-03-31 | 2010-02-23 | Morinaga Milk Industry Co., Ltd. | Drug and food or drink for improving hyperglycemia |
| ES2719098T3 (en) * | 2008-11-19 | 2019-07-08 | Morinaga Milk Industry Co Ltd | Compositions comprising a lofenol |
| KR101434129B1 (en) * | 2008-11-19 | 2014-08-26 | 모리나가 뉴교 가부시키가이샤 | Antioxidant |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH09188630A (en) * | 1995-11-09 | 1997-07-22 | Takeda Chem Ind Ltd | Medicine for improving hepatic function |
| WO2000025803A1 (en) * | 1998-10-30 | 2000-05-11 | Takeda Chemical Industries, Ltd. | Betacellulin protein-containing preparations |
| JP2003113111A (en) * | 2001-10-02 | 2003-04-18 | Kyowa Hakko Kogyo Co Ltd | Medicine for treating diabetes |
| JP2003286185A (en) * | 2002-03-29 | 2003-10-07 | Daily Foods Kk | Squeezed liquid of aloe vera and hypoglycemic agent containing the squeezed liquid as effective ingredient |
| WO2005094838A1 (en) * | 2004-03-31 | 2005-10-13 | Morinaga Milk Industry Co., Ltd. | Drugs, foods and drinks for ameliorating hyperglycemia |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS60214741A (en) * | 1984-04-05 | 1985-10-28 | Toyo Yakushiyoku Kogyo Kk | Hypoglycemic agent |
| JPH05247086A (en) | 1992-01-31 | 1993-09-24 | Kowa Kagaku Kogyo Kk | 1-(3beta-(16beta,28-dihydroxyolean-12-ene)oxy)-2-o-beta-d-glucose-beta-d-glucuronic acid and its production |
| FR2706454B1 (en) | 1993-06-17 | 1995-09-15 | Roussel Uclaf | New 19-Nor steroids, preparation process and intermediates, application as medicaments and pharmaceutical compositions containing them. |
| JP3828953B2 (en) | 1995-05-24 | 2006-10-04 | 日本製粉株式会社 | Lipase inhibitor |
| AU7506396A (en) | 1995-11-09 | 1997-05-29 | Takeda Chemical Industries Ltd. | Composition for improving pancreatic function |
| JPH10330266A (en) | 1997-06-02 | 1998-12-15 | Kotarou Kanpo Seiyaku Kk | Composition having insulin action-enhancing activity |
| US6133440A (en) | 1997-10-10 | 2000-10-17 | Univera Pharmaceuticals, Inc. | Process for the preparation of immunomodulatory polysaccharides from aloe |
| KR20010043558A (en) * | 1998-05-13 | 2001-05-25 | 한센 핀 베네드, 안네 제헤르, 웨이콥 마리안느 | Meiosis regulating compounds |
| EP1174146A4 (en) * | 1999-04-16 | 2003-05-14 | Sumitomo Pharma | PANCREATIC FUNCTION TREATMENT AGENTS |
| US6573299B1 (en) * | 1999-09-20 | 2003-06-03 | Advanced Medical Instruments | Method and compositions for treatment of the aging eye |
| FR2811984B1 (en) | 2000-07-19 | 2004-02-06 | Pharmascience Lab | PROCESS FOR THE PREPARATION OF A FATTY BODY ESTER AND ITS USE IN THE PHARMACEUTICAL, COSMETIC OR FOOD FIELDS |
| RU2192876C2 (en) | 2001-01-30 | 2002-11-20 | Савина Лидия Васильевна | Method of lipid level decrease |
| US6685971B2 (en) | 2001-06-28 | 2004-02-03 | Rongxiang Xu | Method and composition for repairing and promoting regeneration of mucosal tissue in the gastrointestinal tract |
| JP3790686B2 (en) | 2001-08-03 | 2006-06-28 | 独立行政法人理化学研究所 | Hypoglycemic agent |
| AU2003212672A1 (en) | 2003-01-29 | 2004-08-23 | Dal-Hoon Son | Pharmaceutical composition comprising an extract or compounds isolated from elfvingia applanata for the prevention and the treatment of diabetes and diabetic complications |
| EP1644007B1 (en) * | 2003-05-31 | 2012-10-10 | Pharmachem Laboratories, Inc. | Composition comprising one or more phytosterols and/or phytostanols and glucomannan and uses of the composition in treating lipid disorders in individuals with and without type ii diabetes |
| US20050175745A1 (en) * | 2004-02-06 | 2005-08-11 | Jerzy Zawistowski | Method of preservation of a food prodcut and composition comprising one or more phytosterols and/or phytostanols useful for this purpose |
-
2006
- 2006-02-28 RU RU2007122400/15A patent/RU2351340C2/en not_active IP Right Cessation
- 2006-02-28 CA CA2584974A patent/CA2584974C/en active Active
- 2006-02-28 WO PCT/JP2006/303709 patent/WO2006123465A1/en active Application Filing
- 2006-02-28 KR KR1020077009964A patent/KR20070063574A/en not_active Ceased
- 2006-02-28 US US11/576,652 patent/US8101594B2/en active Active
- 2006-02-28 KR KR1020087026409A patent/KR101030247B1/en active Active
- 2006-02-28 EP EP06714846.0A patent/EP1808175B1/en active Active
- 2006-02-28 JP JP2007516211A patent/JP4065017B2/en not_active Expired - Fee Related
- 2006-02-28 CN CN2006800023914A patent/CN101102777B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH09188630A (en) * | 1995-11-09 | 1997-07-22 | Takeda Chem Ind Ltd | Medicine for improving hepatic function |
| WO2000025803A1 (en) * | 1998-10-30 | 2000-05-11 | Takeda Chemical Industries, Ltd. | Betacellulin protein-containing preparations |
| JP2003113111A (en) * | 2001-10-02 | 2003-04-18 | Kyowa Hakko Kogyo Co Ltd | Medicine for treating diabetes |
| JP2003286185A (en) * | 2002-03-29 | 2003-10-07 | Daily Foods Kk | Squeezed liquid of aloe vera and hypoglycemic agent containing the squeezed liquid as effective ingredient |
| WO2005094838A1 (en) * | 2004-03-31 | 2005-10-13 | Morinaga Milk Industry Co., Ltd. | Drugs, foods and drinks for ameliorating hyperglycemia |
Non-Patent Citations (3)
| Title |
|---|
| ABOU-ZEID A.H.S.: "Chemical and Biological Study of the Leaves of some Muca Species", EGYPT. J. PHARM. SCI., vol. 39, no. 4-6, 1998, pages 379 - 398, XP003000295 * |
| MIETTINEN T.A. ET AL.: "Low Synthesis and High Absorption of Cholesterol Characterize Type 1 Diabetes", DIABETES CARE, vol. 27, no. 1, January 2004 (2004-01-01), pages 53 - 58, XP002990129 * |
| YEH G.Y. ET AL.: "Systematic Review of Herbs and Dietary Supplements for Glycemic Control in Diabetes", DIABETES CARE, vol. 26, no. 4, April 2003 (2003-04-01), pages 1277 - 1294, XP002990127 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007034851A1 (en) * | 2005-09-22 | 2007-03-29 | Morinaga Milk Industry Co., Ltd. | Visceral fat accumulation inhibitor |
| US7846905B2 (en) | 2005-09-22 | 2010-12-07 | Morinaga Milk Industry Co., Ltd. | Agent for inhibiting visceral fat accumulation |
| JP2011046708A (en) * | 2009-08-28 | 2011-03-10 | Sinphar Tian-Li (Hangzhou) Pharmaceutical Co Ltd | Use of lanostane and poria extract in treating diabetes |
| WO2023054477A1 (en) * | 2021-09-28 | 2023-04-06 | 森永乳業株式会社 | Method for producing aloe extract |
Also Published As
| Publication number | Publication date |
|---|---|
| KR101030247B1 (en) | 2011-04-22 |
| CA2584974C (en) | 2010-04-20 |
| KR20070063574A (en) | 2007-06-19 |
| CA2584974A1 (en) | 2006-11-23 |
| EP1808175B1 (en) | 2014-11-19 |
| EP1808175A4 (en) | 2007-12-26 |
| US8101594B2 (en) | 2012-01-24 |
| EP1808175A1 (en) | 2007-07-18 |
| CN101102777B (en) | 2011-07-06 |
| RU2351340C2 (en) | 2009-04-10 |
| US20080255077A1 (en) | 2008-10-16 |
| JPWO2006123465A1 (en) | 2008-12-25 |
| JP4065017B2 (en) | 2008-03-19 |
| KR20080108578A (en) | 2008-12-15 |
| RU2007122400A (en) | 2008-12-20 |
| CN101102777A (en) | 2008-01-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8338403B2 (en) | Drug for improving hyperglycemia | |
| RU2353368C1 (en) | Medical product and foodstuff or beverage for pancreas improvement | |
| WO2006123465A1 (en) | Drugs, food or drink for improving pancreatic functions | |
| CN101060850B (en) | Drugs, food or drink for improving pancreatic functions | |
| CN1859917B (en) | Medicines and food or drink to improve high blood sugar | |
| JP4164538B2 (en) | Visceral fat accumulation inhibitor | |
| RU2315601C1 (en) | Medicinal agent and foodstuff or beverage for decreasing hyperglycemia |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
| WWE | Wipo information: entry into national phase |
Ref document number: 11576652 Country of ref document: US |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 2006714846 Country of ref document: EP |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 2584974 Country of ref document: CA |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 1020077009964 Country of ref document: KR |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 2007516211 Country of ref document: JP |
|
| ENP | Entry into the national phase |
Ref document number: 2007122400 Country of ref document: RU Kind code of ref document: A |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 200680002391.4 Country of ref document: CN |
|
| WWP | Wipo information: published in national office |
Ref document number: 2006714846 Country of ref document: EP |
|
| NENP | Non-entry into the national phase |
Ref country code: DE |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 1020087026409 Country of ref document: KR |